12TH ANNUAL EARLY CAREER SCIENTIST CONVENTION

LEADERSHIP AND ENTREPRENEURIAL CONTRIBUTION IN THE NEXT DECADE

SAMRC HEAD OFFICE, CAPE TOWN 17 - 19 OCTOBER 2018 HOSTED BY: RESEARCH CAPACITY DEVELOPMENT (RCD)

TABLE OF CONTENTS 1. Meet our Executive Head of Research Capacity Development 4

2. Message from Division Manager 5

3. Keynote speakers and facilitators 7

4. RCD Funding Categories 16

5. RCD Programmes 18

6. Abstracts 31

7. List of completed scholars 152

3 MEET OUR EXECUTIVE HEAD OF RESEARCH CAPACITY DEVELOPMENT Jeffrey Mphahlele, PhD

Professor Jeffrey Mphahlele, PhD, is Prof Mphahlele is as a member of the the Vice President for Research at the Executive Management Committee of South African Medical Research Council the SAMRC responsible for the Division (SAMRC). He is an elected member of of Research Capacity Development Academy of Science of South Africa (RCD). As such he has a keen interest in (ASSAf) and NRF C1 rated researcher. He the success of the beneficiaries of grants is affiliated to Sefako Makgatho Health and scholarships channeled through Sciences University (formerly MEDUNSA) the Division. Under his leadership, the in Pretoria where he previously served as Division has grown in both vision and an academic for over 20 years in various number of programs. A recent brainchild capacities: Prof Mphahlele’s research of Prof Mphahlele is the Biostatistics interests in prevention and control of human Capacity Development initiative. The viral diseases span a wide range of topics, SAMRC has partnered with the Belgian including viral hepatitis, gastrointestinal Government to help address the scarce viral infections, human papillomaviruses, skills where Biostatistics is concerned in epidemiology of HIV, genomics of South Africa. A few days ago an RFA has infectious diseases and vaccination control been advertised for funding Masters and of infectious diseases. He serves on several PhDs in Biostatistics. It is the vision of governance structures and committees Professor Mphahlele that this is the start including the General Assembly of the of a long fruitful relationship between the European and Developing Countries two countries of South Africa and Belgium Clinical Trials Partnership (EDCTP), Global to develop capacity in the Biostatistics Research Collaboration for Infectious area. Disease Preparedness (GloPID-R) and WHO Scientific Advisory Group of Experts (SAGE) on Polio, Working Group.

4 MESSAGE FROM OUR DIVISION MANAGER

Dr Thabi Maitin

To say that it is a joy to bring once again funder, the SAMRC through RCD and our all SAMRC funded beneficiaries under partners to use this opportunity to remind one roof is an understatement. Seeing our young scientists how absolutely the actual faces of the next generation proud we are of you, how valued you are of Health and Clinical researchers that by the SAMRC and how crucial it is that South Africa is developing through this you succeed. South Africa needs you to Division and other entities in South African succeed and get your degrees, especially Universities is truly inspiring. the PhDs, and as research has shown, help to change the economy of South Africa. It When the Masters and PhD scholars is a well-documented fact that the number are away at their universities during the of PhDs in a country is one of the indicators course of the year, it is easy to forget just of the success of that country’s economy. how important this mission of capacity development is. It is also easy to lose The financial year of 2017/18 till to date awareness of the urgency of this mandate. has recorded an impressive increase in Thus, an opportunity to meet face to performance by almost all indicators. face at our annual conference with these However, it is the number of 25 graduates bright, young people is very important so in this period, mostly PhDs coming out of that the mandate and its urgency is kept all the post graduate programs that stands fresh in our minds out as something for all parties to pat themselves at the back for. Similarly, the The Early Career Scientist Convention number of publications, briefs and other (ECSC) provides an opportunity to network, research outputs has increased both in share experiences, share successes and quality and number. challenges, and have healthy competition as a generation of upcoming young RCD itself is growing in the number of scientists. Equally, it is important for the staff as funding programs increase in

5 number and complexity. Today we boast and more particularly the abstracts by established partnerships with various scholars for the Convention. I will be hard countries to help us develop capacity in pressed to find a matching replacement. strategic areas such as Vaccinology (with But I thank Jean so profusely for the Switzerland), Biostatistics (with Belgium) to warmth that was felt not just by myself name a few. In terms of staff resource, RCD over the years working with her, but by the is happy to have welcomed Dr Anniza De scholars themselves. Some actually turned Villiers who will be overseeing the writing her into their own personal editors, and of scientific publications of RCD work and Jean smiled all this away…thank you Jean! outputs. That way, South Africa and all other You are always welcome for a coffee in my stakeholders will know what the SAMRC office for as long as I am at SAMRC. is doing to grow the next generation of scientists in health /clinical research, and Lastly, to our Masters, PhDs, Post docs, how SAMRC’s funding portfolio continues Mid-Career Scientists, PIs from the RCDI to be innovative. We have also welcomed (aka HDIs), Vaccinology cohorts, the new Ms Colleen Van Wyk who is assisting with Biostatistician PhDs, National Medical streamlining work flow and processes scholars at UCT& Pretoria, Medical PhDs between the Division Manager’s office and from the special node at Wits- I know all Program administration desks. This is almost all of you by name or other, and invaluable addition to the Division and we I have a soft heart for each of you to be are working towards increasing the staff a the bright stars that you are. SAMRC little more in order to increase efficiency. does not support mediocrity, so you know “if you are on our roll, you rock!!!”. All It is with a heavy heart that I say a very the best for 2019/20. Remember, don’t sad goodbye to Ms Jean Fourie come end chew through your (sometimes imagined) of 2018/19. I have a fairly long experience difficulties alone, my office is always open working in academia, but I have met very to you. few people who have the excellence that I have enjoyed with Jean editing RCD work

6 CONTRIBUTORS

KEYNOTE SPEAKERS 1. Prof Nokwanda Pearl Makunga – University of Stellenbosch 2. Mr. Kenneth Mhlongo – Custocare Consultants 3. Mr Zuko Mandlakazi – Project Manager

MASTERCLASS CONVENERS Thesis Writing and Presentation Skills 1. Mr. Alfred Thutloa – Head of Communication (SAMRC) 2. Dr Lawrence Mabasa – Biomedical Research and Innovation Platform (SAMRC) • Dr Ntevheleni Thovhogi – Biomedical Research and Innovation Platform (SAMRC) • Dr Ibrahim Samodien – Biomedical Research and Innovation Platform (SAMRC)) • Dr Tarryn Wilmer – Biomedical Research and Innovation Platform (SAMRC) 3. Dr Tamara Credo – Cochrane South Africa (SAMRC)

SCIENTIFIC PRESENTATIONS SESSION CHAIRS 1. Dr Alison Wiyeh – Seasoned Scientist Cochrane South Africa 2. Dr Jillian Hill – Non-Communicable Research Unit (SAMRC) 3. Dr Nadine Burnhams – Alcohol, Tobacco and other Drug Research Unit (SAMRC) 4. Ms Nontuthuzelo Somdyala – Burden of Diseases Research Unit (SAMRC) 5. Ms Shibe Mhlongo – Gender and Health Research Unit (SAMRC)

WITH GRATEFUL THANKS… Research Capacity Development (RCD) would like to acknowledge the following colleagues who have been contributing to the work of RCD diligently and selflessly over the years. They are indeed the extended RCD team:

SAMRC Portfolio Contribution and Role at RCD Prof Johan Director – Biomedical Research and Chair: RCDs Grants and Scholarships Louw Innovation Platform (BRIP) Selection Committee (MSc/PhD/ Postdoc programmes) Prof Andre Director – Non-Communicable Diseases Chair: RCDs Grants and scholarships Kengne Research Unit (NCDRU) Selection Committee (MD. PhD programme) Dr Shaheen Research Scientist – University of Cape Member: RCDs Grants and Mowla Town (UCT) Scholarships Selection Committee Ms Jean Language Practioner/ Senior Scientist Editor: RCD print and other resources Fourie

Ms Sumaya Senior Legal Advisor - SAMRC Advisor: RCD legal matters, processes, Behardien and resources Mr Clive Grants Manager – Grants, Innovation, Member: RCDs Grants and Glass and Product Development Scholarships Selection Committee Ms Business Partner: Project Management Oversight: RCD Financial matters, Noluthando and Accounting Office SAMRC processes, and budgets Sikhutshwa 7 KEYNOTE SPEAKERS

and senior management levels for more than a decade in various industries in private and public sectors. Over the years he has amassed valuable governance and strategy skills having served on boards and committees of diverse institutions. Based on his passion for education, he worked part-time for Institutions of Higher learning, MANCOSA tutoring MBA students and UNISA tutoring Business Management, undergraduate students.

As a seasoned entrepreneur who owned and managed business entities across BIO-SKETCH business sectors, Kenneth has a passion MR. KENNETH MHLONGO for setting up and supporting emerging businesses in all compliance and Kenneth Mhlongo holds an MBA from optimisation areas. Hence, he founded the North-West University and is currently enrolled for LLB (3rd year) with UNISA. Custocare Consultants to realise his dream. He is the Founder and Managing Director In between, he does a bit of motivational of Custocare Consultants, a Business speaking and is a strong advocate for Consulting firm offering among other the development of sustainable SMMEs things accounting, tax, BEE verification, as he believes they are a solution to business start-ups, financial advisory, the unemployment monster facing our business financing, business advisory and country. mentoring services focusing on small, In line with our 2018 theme Kenneth medium and micro enterprises (SMMEs). will talk about, “Leadership geared for Kenneth is an all-around and astute creating and growing sustainable SMMEs Business Manager who has held several contributing towards the reduction of management positions at junior, middle unemployment in the next decade”.

8 was aimed at micropropagation and genetically modifying Thapsia garganica an umbelliferous Mediterranean species which is now known as an ‘anticancer hand- grenade’. She used a multidirectional approach that combines the areas of biotechnology, ethnopharmacology and phytochemistry. The research is essential to establish a system for producing plantlets that would lead to commercialisation and conservation of the species. To better understanding of the molecular mechanisms governing the synthesis of BIO-SKETCH secondary compounds in these plants using a functional genomics approach, PROF. NOKWANDA PEARL they apply high-end technologies thus, (NOX) MAKUNGA adding value to local flora intimately Nokwanda Makunga is a Professor of linked with traditional plant knowledge. Biotechnology at Stellenbosch University. Prof Makunga has won prestigious She grew up in Alice in the Eastern Cape awards such as the National Science and and attended a private boarding school Technology Forum Distinguished Young in Grahamstown. She studied at the then Black Researcher Award in 2011, and the Natal University in Pietermaritzburg and TW Kambule NRF Research Award. In majored in Biochemistry and Microbiology. 2017, she was a Fulbright scholar at the Her interest in biochemistry and genetics University of Minnesota, Minneapolis. She led to entering a postgraduate programme at the Research Centre for Plant Growth worked with Jerry Cohen on medicinal and Development under the leadership of plants from the Eastern Cape and studied Prof J van Staden. She obtained her PhD the Stevia plant. She holds a patent for at the University of KwaZulu-Natal in 2004, vegetative plant propagation. She has working on the molecular biology of plants. acted as honorary secretary, Vice President and President of the South African In 2005, she was recruited by Stellenbosch Association of Botanists Council. University as the first black female lecturer in the Science Faculty and became Prof Makunga is a passionate science an Associate Professor in 2014. She communicator, and her talk, “Exploiting established a new research direction our botanical wealth to contribute to the utilising various biotechnological tools health and the bio-economy” should including Cape medicinal flora, which surely demonstrate this.

9 Festival in Austria, at Eureka Innovation Week in Sweden and his participation at the Venture Leaders in Switzerland. The experience has helped him shape Senso as a start-up in developing a wearable wrist device, specifically for use among the deaf or hard hearing persons, which he is currently building.

Zuko’s focus is on applying lean methodologies and basic social anthropology to do research, customer development and feedback, then to use all BIO- SKETCH the data acquired for product reiteration. Other responsibilities include innovation MR. ZUKO MANDLAKAZI leadership, monitoring progress Zuko Mandlakazi studied banking and towards achieving objectives and being accountancy. He has worked and acquired accountable for all the start-up activities. experience as an Accounting Officer and as a Project Manager from Guarantee He has received several awards and Trust, Absa Bank, Eskom and EduLoan. acknowledgements of which the Top 150 brightest young minds in South Africa He attended workshops on business features. management at Gibs Business School in South Africa, and masterclasses With his title, “Bootstrapping the dream”, and leadership innovation, customer Zuko will focus on learning insights, while development and business management bootstrapping for Senso, which started as abroad. Some of these are, at the Pioneers an idea to what it currently is.

10 MASTER CLASS CONVENERS

organisation (NGO), also Marketing and Strategic Partnerships Manager for a hospitality group in Cape Town and Mauritius.

He also has experience as a Communications Specialist focusing on health communications for MMI Holdings. His NGO experience includes coordinating the philanthropy programme for the South African Institute for Advancement and coordinating communications for mothers2mothers, a non-profit organisation that employs, BIO-SKETCH trains and empowers HIV-positive women as community health workers. MR. ALFRED THUTLOA Alfred’s qualifications include a master’s Alfred Thutloa is the Head of Corporate degree in Intercultural Communication, & Marketing Communications at the a postgraduate degree in Cultures and South African Medical Research Council Heritage Studies and a bachelor’s in (SAMRC). Alfred joined the SAMRC in international studies from Stellenbosch April 2017 as the Corporate Relations University. He is completing a PhD Manager. He was the Head of Marketing in linguistics with a focus on health and Communications for a pan-African communication at the University of the research and advocacy non-governmental Western Cape.

11 BIO-SKETCH BIO-SKETCH DR LAWRENCE MABASA DR.TAMARA KREDO

Born and raised in Limpopo, Dr Lawrence Tamara Kredo is a Senior Specialist Mabasa is a former Fulbright Scholar Scientist at Cochrane South Africa, based who obtained his MS and PhD degrees at the South African Medical Research in Nutritional Physiology at North Dakota Council, Tygerberg. She is a medical State University (NDSU), Fargo, USA, doctor with a specialist qualification in under the supervision of Prof Chung Clinical Pharmacology. She works in the Park. His research centred on the role of field of evidence-informed healthcare, in maternal nutrition (mainly canola oil and particular, evidence synthesis. Her research methyl donor nutrients) on mammary and focus includes exploring the South African breast cancer biology in the offspring. primary care guideline landscape and Dr Mabasa has authored/co-authored developing partnerships for enhancing eight peer-reviewed articles published guideline activities in South Africa. Other in Journals such as Carcinogenesis areas of work include supporting capacity and Nutrition and Cancer, while also development initiatives for evidence- contributing approximately R10 million based healthcare in South Africa and worth of research grant during his stay at Africa through the work of the Cochrane NDSU. Upon returning to South Africa, African Network along with optimising he spent a year at the University of Cape communication of evidence to relevant Town in Prof Sharon Prince’s laboratory as a stakeholders to inform healthcare Postdoc. He then joined the South African decision-making. Medical Research Council (SAMRC) as a Postdoctoral Fellow in 2017. Currently, Dr Mabasa is co-supervising four PhD students in Dr Rabia Johnson’s laboratory at the SAMRC.

12 FACILITATORS

BIO-SKETCH BIO-SKETCH DR ALISON WIYEH DR JILLIAN HILL

Alison Wiyeh is a seasoned scientist at Jillian Hill is a Senior Scientist appointed Cochrane South Africa, an intramural Unit at the Non-Communicable Diseases of the South African Medical Research Research Unit at the South African Medical Council (SAMRC). She holds a Doctor of Research Council, Tygerberg. Jillian Medicine degree from the University of qualified at the University of the Western Buea Cameroon and a master’s degree in Cape obtaining the degrees, B. Psych, Clinical Epidemiology from Stellenbosch MPH, and PhD Public Health. Currently, University. She is a passionate clinician, she is the Project Manager/Coordinator driven by her determination to ensure that of the South African Diabetes Prevention health care decisions, especially in Africa, Programme. The overall purpose of are evidence-informed. She has been this project is to develop and evaluate involved in research projects that have a culturally-relevant model of diabetes influenced national health care decisions. prevention for South Africa using evidence Her main area of interest is maternal from successful diabetes prevention and child health, with a strong emphasis effectiveness and implementation on vaccine-related research. She is also programmes. Her research focus in recent involved with capacity building on the years has been in the food environment, conduct and use of Cochrane systematic healthy lifestyles and non-communicable reviews locally and in other countries diseases prevention. Her interests lie within Africa in community participatory research, interventions and project evaluation.

13 and presented at conferences locally and internationally. She has co-authored a book titled Alcohol, Drugs and Employment. She has advised local, provincial and national government on issues related to alcohol and drug abuse prevention and policy and has acted as a technical advisor and consultant to the United Nations Office on Drugs and Crime (UNODC) on the drafting of guidelines for substance abuse prevention initiatives in the workplace as well as the UNODC International Prevention Standards for Drug Use. She has taught various

BIO-SKETCH undergraduate and postgraduate courses DR NADINE BURNHAMS at the University of Cape Town and Stellenbosch. Dr Burnhams is currently Dr Nadine Harker Burnhams is employed the national head of the South African as a Specialist Scientist in the Alcohol, Community Epidemiology Network on Tobacco and other Drug Research Unit Drug Use (SACENDU), a project that aims of the South African Medical Research to provide community-level public health Council. She completed her PhD at the surveillance of alcohol, tobacco and other University of Cape Town and currently drug (ATOD) use trends and associated holds the position of honorary research consequences. Her specific interests are associate at the UCT School of Public in improving the quality of substance Health and Family Medicine. She has abuse prevention services, monitoring authored and co-authored peer-reviewed and evaluating the performance and journal articles, technical research outcomes of such services, and designing reports, and policy documents on the and implementing substance abuse topic of substance abuse prevention, prevention services for the work sector.

14 Eastern Cape Province Cancer Registry which she manages; the only functional population-based cancer registry in South Africa. Development and survival of this registry was the result of the strong relationship that Ntuthu developed and maintained between the SAMRC and project collaborators at the Eastern Cape Department of Health, Cancer Association of South Africa, and Eastern Cape community, specifically traditional leaders. Ntuthu has extensive training and practical experience in cancer registration, methods and principles. Direct sharing BIO-SKETCH of knowledge through formal teaching MS. NONTUTHUZELO IRIS remains her key responsibility as an established scientist. As a recognised MURIEL SOMDYALA cancer surveillance expert, she has been Ntuthu is a graduate nurse and midwife invited to present her work in local and who specialised in nursing administration international meetings, workshops and and education. She joined the South conferences She teaches Public Health African Medical Research Council (SAMRC) Masters students at the University of Cape in 1998 as a Research Technologist. She Town and has a team which is mentored started setting up a cancer registry to and mainly developed in the field of public support research conducted by SAMRC health and cancer surveillance. Her focus is scientists in understanding why there is to reduce unnecessary premature deaths a high risk of oesophageal cancer in a caused by cervical cancer in women, and particular population group. Currently, her main interests are cancer surveillance, she is a Senior Scientist and Head of prevention and early detection.

15 Shibe Mhlongo is a data manager and statistician for the Gender and Health Research Unit (GHRU) RICE study, based in Pretoria. She holds a degree in BSc Mathematics and Statistics from the University of Zululand and an Honours degree in Statistics from the University of Western Cape. She is currently working towards a Master’s in Biostatistics with the University of Stellenbosch, and her interest area is in the analysis of longitudinal studies. She works closely with Drs Carl Lombard (Biostatistician) and Naeemah Abrahams (Deputy Director, GHRU) on the BIO-SKETCH impact of rape in women on HIV acquisition MS. SHIBE MHLONGO and retention and linkages to car.

16 RESEARCH CAPACITY DEVELOPMENT (RCD) STAFF Left to right: Ms Pumla Zonke, Ms Philistia Joshua, Dr Anniza de Villiers (senior scientist), Dr Thabi Maitin (Division Manager), Ms Colleen Van Wyk, Mr Thobile Mabuya, as well as Jorene Naidoo (insert)

RESEARCH CAPACITY DEVELOPMENT (RCD) FUNDING CATEGORIES 2018/19 Scholarship Value of Purpose/ Administrators program/grant Target Group scholarship/ importance type grant Mr. Thobile SAMRC Excellent Incentive early R350 000.00 p.a Mabuya Intramural Postdoctoral investigators x 5 years (Postdoctoral) support career Programme. development program. Mr. Thobile SAMRC Clinician Post MBChB/ Response to R500K p.a salary Mabuya Researcher D.D. S stugying dearth of MD. contribution x Development towards their PhD cadre 4 yrs. MD. PhD PhD degree within the health programme research team in SA and Globally Ms. Jorene SAMRC MSc’s and PhDs Directly supports PhD: R200K Naidoo Internship research training transformation. p.a x 3yrs. MSc scholarship for generic black In-house R160K p.a x 2yrs programme scientists research (package incl. skills transfer tuition) program.

17 Scholarship Value of Purpose/ Administrators program/grant Target Group scholarship/ importance type grant Ms. Jorene SAMRC Once-off, Directly support Up to R250K Naidoo Research last year PhD transformation, p.a. x 1yr. Development funding for to help fast track Grant strategic PhDs PhD completion by university/ for senior staff health sector at institutions staff or at strategic places/level of employment Ms. Pumla National Health Doctoral (and Gold standard Various: Zonke Scholarship Masters where Public Private equivalent to Programme compelling) Partnership after tax take (NHSP) Research for PhD home package training development for profession Internships in SA. according to SA for SA young (Stakeholders, Government Scientist NHRC, Full-time Cost NDoH, PHEF of Employment and SAMRC figures. partnership) Ms. Philistia SAMRC Target Directly support R1ML p.a. Joshua Research institutions transformation: per selected Capacity rather than to develop university for 5 Development Individual research years Initiative (RCDI) Researcher capacity and to programme Capacity work towards at Selected Development: closing the Universities Project leaders gap in rate of in selected generation of under resourced knowledge institutions between established research intensive universities and under resourced universities Ms. Philistia Mid-Career Excellence Mid- R1.2ML for the Joshua Scientist Career Scientist 1st year and Programme development R1.5ML for the program in 2nd year five strategic research areas

18 EARLY CAREER SCIENTIST CONVENTION 2018 PROGRAMME Day 1: Masterclasses 17 October 2018 09h30 – 10h00 Arrival/Registration 10h00 – 12h00 Masterclass 1 (Plenary): Taking science to the masses and building effective communication (Convener – Mr Alfred Thutloa) 12h30 – 13h15 Lunch 13h15 – 14h15 Masterclass 2: Thesis writing Masterclass 3: Presentation skills (Convener - Dr Lawrence Mabasa) (Convener - Dr Tamara Kredo) 14h15 – 14h30 Tea break 14h30 – 15h30 Master class 1 (cont.) Masterclass 2 (cont.) 16h00 – 16h30 Shuttle to Hotel

Day 2: Convention 18 October 2018 Session 1: Opening ceremonyAuditoriumProgramme Director: Dr Verusia Chetty 09h30 – 10h00 Arrival/Registration 10h00 – 10h10 Welcome and Housekeeping Dr Thabi Maitin 10h10 – 10h30 Welcome address Prof Mark Cotton 10h30 – 11h00 Keynote 1- Exploiting our botanical Prof Nokwanda Makunga wealth to contribute to health and the bio economy 11h00 – 11h20 Tea break Session 2: Oral Presentations (Parallel sessions) Parallel session 1: Parallel session 2: Health Non-communicable systems/social science diseasesAuditoriumFacilitator: RestaurantFacilitator: Dr Jillian Hill Dr Nadine Harker 11h20 – 11h30 Introduction Introduction 11h30 – 11h40 P1.1: Prevalence of obesity, P2.1:“Codeine Is My Helper”: hypertension and erectile Misuse of and Dependence on dysfunction among HIV –ve and Codeine-Containing newly diagnosed HIV +ve ART Medicines in South Africa. S Dada naïve patients. V Mbombela 11h40 – 11h50 P1.2: A 12-week exercise P2.2: Sustainable financing intervention improves insulin options for mental health care sensitivity in sedentary black obese in South Africa: findings from a South African women: The role of situation analysis and key informant ectopic lipid content. M Fortuin-de interviews. S Docrat Smidt

19 11h50 - 12h00 P1.3: Nanoformulation of Artimisia P2.3: Impact of Nyaope on physical afra and its potential biomedical health and organ functions. K applications in type 2 Diabetes. B Mokwena Pearce 12h00 - 12h10 P1.4: Effect of different P2.4: An intersectoral collaboration formulations of Banana peel and model for the implementation of Grape seed in preventing obesity in the integrated school health policy Sprague Dawley rats. O Aboyade in the Eastern Cape Province, South Africa. S Mnwana 12h10 -12h20 P1.5: Understanding the P2.5: Health related quality of life in mechanism of Doxorubicin-induced patients treated with antiretroviral Cardiotoxicity. N Sangweni therapy only versus chemotherapy and antiretroviral therapy for HIV-associated Kaposi sarcoma: a randomized control trial. F Shaik Session 3: Plenary sessionTopic: Leadership and Entrepreneurial Contribution in the next DecadeAuditoriumFacilitator: Dr Verusia Chetty 12h20 - 13h00 Keynote 2 - Bootstrapping the Mr. Zuko Mandlakazi dream 13h00 - 13h30 Award Ceremony Dr Thabi Maitin and Ms. Nontuthuzelo Somdyala 13h30 Shuttle to Hotel 14h00 Marcos Event

Day 3: Convention 19 October 2018 09h30 – 10h00 Arrival/Registration Session 4: Oral Presentations (Parallel sessions) Parallel session 3: Molecular/Bio Parallel session 4: Communicable SciencesAuditoriumFacilitator: diseasesRestaurantFacilitator: Ms. Shibe Mhlongo Dr Allison Wiyeh 10h00 – 10h10 Introduction Introduction P3.1: Proteomic analysis of P4.1: Simulation and modelling geometrically and ethnically of longitudinal HIV viral load 10h10 – 10h25 classified human hair in a South measures during pregnancy and African cohort. H Adeola breastfeeding. T Glass P3.2: Design, synthesis and in vitro P4.2: Knowledge, Attitudes and bio-analytical tests of new chemical Practices on Schistosomiasis in Sub- 10h25- 10h40 entities as CYP17A1 inhibitors: Saharan Africa: A systematic review. targeting prostate cancer. NJ H Sacolo Gumede

20 P3.3: Investigation of the P4.3: Percutaneous pericardioscopy influence of genetic variation on in a population with a high the expression efficiency of the prevalence of tuberculous 10h40 - 10h55 promoter region of SLC47A2/ pericarditis – improving the MATE-2K gene. C Masilela diagnostic yield and advancing the time to diagnosis. C Kyriakakis P3.4: Whole-genome Transposon P4.4: Impact of Implementation of Mutagenesis to Elucidate the Gene Xpert Ultra on TB diagnosis in 10h55 – 11h10 Genetic Requirements for Vitamin South Africa. H Moultrie B12 Biosynthesis and Assimilation in Mycobacteria. R Mbau P3.5: Genetic variation within P4.5: Application of the IMVACC the coding region of CCR5 in program in the workplace. T Khoza 11h10 – 11h25 Chronically HIV-1 infected South African individuals. N Matume 11h25 – 11h35 Tea Break

Session 5: Plenary sessionAuditoriumProgramme Director: Dr Verusia Chetty 11h35– 12h10 Keynote 3 - Leadership geared for Mr. Kenneth Mhlongo creating and growing sustainable SMMEs contributing towards the reduction of unemployment in the next decade 12h10– 12h30 Closing remarks and thank you Dr Thabi Maitin, Ms. Nontuthuzelo Somdyala 12h30 – 13h15 Lunch 13h15 Delegates depart to airport

21 SAMRC INTRAMURAL (POSTDOCTORAL) PROGRAMME No Initials Surname University/ Abstract Tittle Research Unit 1. M. Aboyade Tshwane University Effect of different formulations of of Technology banana peel and grape seed in preventing obesity in Sprague Dawley rats 2. J. Bantjes Stellenbosch We try our best, but it’s probably University not our best”: Health professionals’ experience of providing emergency care to self-harm patients in a South African hospital 3. T. Brombacher University of Cape The role of CD4+ T-cell subsets in Town cognitive function 4. C. Ealand University of the Resuscitation-promoting factors are Witwatersrand required for Mycobacterium smegmatis biofilm formation 5. C. Ginsburg University of the Health-care utilisation and internal Witwatersrand migration in rural and urban South Africa 6. B. Sumner Alcohol, Tobacco ‘We are here for our patients’ – and Other Drugs resilience amidst challenges in primary Research Unit care managers 7. W. Chirinda Health Systems Unmet need for contraception, Research Unit unplanned pregnancy and contraceptive use among HIV-infected and HIV-uninfected women in South Africa 8. J. Coetzee Gender and Health Modelling HIV and associated factors Research Unit among sex workers in South Africa

9. J. Dietrich Health Systems A baseline investigation of factors Research Unit associated with viral suppression among young women and girls from the HERStory Study in ten South African districts 10. P. Dludla Biomedical Investigating a dose-dependent effect Research Innovation of palmitate and simvastatin on cell and Platform viability and production of reactive oxygen species using an in vitro model of diabetic cardiomyopathy 11. M. Klopper Centre for Isoniazid resistance determination: Tuberculosis challenges in practice Research Unit

22 12. A. Mutshambele Tuberculosis The potential of single nucleotide Platform (PTA) polymorphisms within virulence genes as lineage and sub-lineage markers of Mycobacterium tuberculosis 13. C. Naidoo Centre for Oral, airway and gut microbial Tuberculosis communities are altered in patients Research Unit with active tuberculosis 14. A. Ngwane Centre for Proteomic analysis reveals that Tuberculosis sulfamethoxazole induces oxidative Research Unit stress in M. tuberculosis 15. B. Pearce University of the Nanoformulation of Artemisia afra and Western Cape its potential biomedical applications in type 2 diabetes 16. T. Sylvester Centre for Novel qPCR assays for the Tuberculosis measurement of immune gene Research Unit expression in African lion (Panthera leo) whole blood 17. N. Thovhogi Biomedical Effects of rooibos phenolic compounds Research Innovation on microbiota regulation and and Platform prevention of the metabolic syndrome

SAMRC CLINICIAN RESEARCHER CAPACITY DEVELOPMENT (M.D PHD) PROGRAMME No Initials Surname University/ Abstract Tittle Research Unit 18. M. De-Smidt University of Cape A 12-week exercise intervention Town improves insulin sensitivity in sedentary black obese South African women: The role of ectopic lipid content 19. L. Githinji University of Cape Longitudinal changes in spirometry in Town perinatally HIV-infected adolescents on antiretroviral therapy in Cape Town, South Africa 20. J. Holness Stellenbosch The reliability of estimated glomerular University filtration rate in South African children 21. A. Jabar University of Cape The introduction of violence and injury Town observatories suggests a reduction in violence-related injury in adult populations. A systematic review and meta-analysis 22. W. Jassat University of the The decentralised drug-resistant TB Western Cape programme in South Africa: From policy to implementation

23 23. C. Kyriakakis Stellenbosch Percutaneous pericardioscopy in a University population with a high prevalence of tuberculous pericarditis – improving the diagnostic yield and advancing the time to diagnosis 24. C. Marsay University of Postnatal mood and socio-economic Witwatersrand context among low-income women in Johannesburg, South Africa 25. H. Moultrie University of Impact of implementation of Gene Witwatersrand Xpert Ultra on TB diagnosis in South Africa 26. F. Shaik University of Plasma Kaposi’s sarcoma herpesvirus KwaZulu-Natal DNA as a prognostic biomarker 27. L. Van den Stellenbosch Hair cortisol levels in posttraumatic Heuvel University stress disorder patients versus controls 28. E. Zitha University of Cape A prospective study of the Town epidemiology of severe cutaneous adverse drug reactions and associated neuropsychiatric sequelae

SAMRC INTERNSHIP SCHOLARSHIP PROGRAMME (ISP) No Initials Surname University/ Abstract Tittle Research Unit 29. Z. October Biomedical Genetic polymorphisms and in vitro Research and analysis of SLC22A2 and SLC47A2 Innovation Platform promoters in the Xhosa population 30. J. Arries Stellenbosch Molecular characterisation of proteins University involved in iron-sulphur cluster assembly in mycobacteria 31. I. Boshielo University of Plasma cytokine biomarkers to predict Witwatersrand Tuberculosis treatment response 32. N. Ellman University of Cape Adipose tissue antioxidant expression Town in visceral and subcutaneous abdominal depots and the association with cardiometabolic risk factors in an obese population 33. N. Ellman University of Cape Effect of Roux-en-Y gastric bypass Town surgery versus a conventional weight- loss programme on cardiometabolic risk factors at one and six months post- intervention 34. N. Hlengwa Biomedical Influence of Lessertia frutescence Research and and Echinacea purpurea on the Innovation Platform bioavailability and metabolism of ethinylestradiol based contraceptives

24 35. L. Keet Stellenbosch The effects herbal teas (Rooibos University and Honeybush) in the regulation of inflammatory responses during skin carcinogenesis 36. N. Khuboni Biomedical An anti-steatotic effect of Aspalathin- Research and rich green Rooibos extract on oleic acid Innovation Platform induced steatosis in C3As 37. S. Mabhida University of the Understanding the role inter- Western Cape individual genetic variation plays in the development of uncontrolled hypertension in patients with concomitant type 2 diabetes mellitus at Tygerberg Academic Hospital, Western Cape South Africa 38. N. Mabuza University of Background qualifications, self- KwaZulu-Natal perceived competencies and leadership development practices among public-sector hospital managers in KwaZulu-Natal 39. N. Malaza University of The association between Witwatersrand polymorphisms in the vitamin D receptor and metabolizing enzyme genes and type 1 diabetes mellitus in the South African Indian population 40. C. Masilela University of the Investigation of the influence of genetic Western Cape variation on the expression efficiency of the promoter region of SLC47A2/ MATE-2K gene 41. R.D. Mbau University of Cape Whole-genome transposon Town mutagenesis to elucidate the genetic requirements for vitamin B12 biosynthesis and assimilation in mycobacteria 42. S. Modiba University of Development and validation of Witwatersrand antiretroviral drug levels for therapeutic drug monitoring using dried blood spots 43. H. Mutayhatsindi Stellenbosch Prospective evaluation of candidate University host immunological biosignatures as tools for the diagnosis of TB disease 44. Y. Ntamo Biomedical Metabolic profile of rat Insulinoma Research and beta-cell spheroids (INS-1) Innovation Platform

25 45. C. Ntsapi Stellenbosch Sustained autophagic flux with cell University death onset in an in vitro model of Alzheimer's disease 46. E. Oduwole Stellenbosch Investigating vaccine hesitancy and University validating a measuring tool in the Western Cape Province 47. S. Pitts Stellenbosch Genome-wide associations between University host genotypes and M. tuberculosis 48. N. Sangweni Biomedical Prevention of Doxorubicin-induced Research and cardiotoxicity: A mechanistic study Innovation Platform 49. M. Shaku University of A peptidoglycan recycling and Witwatersrand amidation enzyme in Mycobacterium tuberculosis as a new drug target for tuberculosis

NATIONAL HEALTH SCHOLARSHIP PROGRAMME (NHSP) No Initials Surname University/ Abstract Tittle Research Unit 50. T. Assegaai University of the Supervision system of WBOT in North Western Cape West Province Districts 51. K. Barnard Stellenbosch Diversity and ecology of astroviruses in University South African bats 52. W. Barnett University of Cape Maternal exposure to trauma and child Town adverse growth outcomes in a South African birth cohort 53 K. Berner Stellenbosch Biomechanical analysis of specific University motor impairments contributing to early functional decline in adults living with HIV/AIDS: sub-study to the Cape Winelands HAART to HEART/ EndoAfrica study 54. K. Brittain University of Cape Patterns and predictors of HIV-status Town disclosure among pregnant women in South Africa: Dimensions of disclosure and influence of social and economic circumstances 55. B.S. Carpenter University of Kwa- Understanding treatment Zulu Natal individualisation and its impact on study design and analysis 56. S. Dada Alcohol, Tobacco Codeine is my helper”: Misuse of and and Other Drugs dependence on codeine-containing Research Unit medicines in South Africa

26 57. A. Damons Stellenbosch Introducing an arteriovenous fistula University pre-cannulation assessment care- bundle to reduce complications in patients with an arteriovenous fistula on haemodialysis 58. S. Docrat University of Cape Sustainable financing options for Town mental health care in South Africa: findings from a situation analysis and key informant interviews 59. L. Frigati University of Cape Multisystem impairment in perinatally Town HIV-infected South African adolescents on ART 60. P. Gina University of Cape In vivo and in vitro studies to Town investigate the role of autophagy in human tuberculosis 61. T. Glass University of Cape Simulation and modelling of Town longitudinal HIV viral load measures during pregnancy and breastfeeding 62. D. Govindasamy Health Systems Well-being among youth living with Research Unit and without HIV in South Africa: A health economic perspective 63. H.G Sacolo University of Knowledge, attitudes and practices on KwaZulu-Natal schistosomiasis in sub-Saharan Africa: A systematic review 64. L.J. Nzuzi Khuabi Stellenbosch Factors influencing high school re-entry University and school participation following the onset of a traumatic brain injury 65. K. Kgoadi University of Cape Dendritic cells and other antigen Town presenting cells induce protective Th1 immunity in mice infected with central nervous system tuberculosis 66. H. Koch University of Becoming an interventionist-researcher KwaZulu-Natal during the research process 67. G. Mahumane University of 3D scaffold for neural tissue Witwatersrand engineering 68. S. Manie University of Cape Pulmonary rehabilitation for people Town with tuberculosis in a high HIV-positive setting: A randomised control trial 69. K. Montjane University of Cape Pharmacogenetics of tenofovir Town 70. M. Mutemwa University of the Developing an education programme Western Cape designed to improve quality of life of people living with HIV on antiretroviral therapy in the Johannesburg Metropole

27 71. M. Nglazi University of Cape An analysis of overweight and obesity Town in South Africa: The case of women of childbearing age 72. J. Nothling Stellenbosch Genome-wide differentially methylated University genes associated with PTSD in female rape survivors 73. Z. Ogle Stellenbosch The quality of life of primary health care University patients diagnosed with hypertension and/or diabetes in the Eastern Cape, South Africa 74. M. Osman Stellenbosch Finding former tuberculosis patients University - a high-risk group for tuberculosis- associated morbidity and mortality in Cape Town, South Africa: A pilot study 75. A. Papadopoulos University of A novel metallo-endopeptidase Witwatersrand required for peptidoglycan remodelling during osmolarity changes in M. tuberculosis 76. S. Pasche Stellenbosch Harm-reduction in the management University of adolescent self-harm: ethical and practical considerations in a South African context 78. N.J. Philips University of Cape HIV-associated cognitive disorders Town in children and adolescents: methodological investigations and validating a quick screening tool 79. R.D. Pietersen Stellenbosch Mouse macrophages upregulate University Mx1 and Mx2 upon infection with mycobacteria 80. C.M. Pule Stellenbosch Deciphering the physiological state University of drug resistant Mycobacterium tuberculosis strains 81. C. Schutz University of Cape High early mortality in patients Town hospitalised with HIV-associated tuberculosis: Characterising the immune response associated with death 82. N.V. Sibiya University of Cape Understanding and defining blood Town biomarkers of subclinical tuberculosis and their relationship to inflammation at the site of disease

28 SAMRC RESEARCH DEVELOPMENT INITIATIVE PROGRAMME (RCDI) No Initials Surname University/ Abstract Tittle Research Unit 83. N.E. Bam Walter Sisulu Determinants of type-2 diabetes University mellitus among HIV/AIDS patients on antiretroviral drugs in the OR Tambo district, South Africa 84. T. Apalata Walter Sisulu Factors associated with recent University unsuppressed viral load in HIV-1- infected patients receiving first-line antiretroviral therapy in an NHI pilot district in Eastern Cape, South Africa 85. T. Apalata Walter Sisulu Task-shifting for antiretroviral treatment University delivery and quality of HIV/AIDS care initiated by nurses at primary health- care level in Eastern Cape, South Africa 86. A. Boggenpoel University of the The proposed adaptation and Western Cape implementation of acute care clinical guidelines in the management of traumatic spinal cord injuries for the South African context: A Delphi consensus study protocol 87. P.K.P Chokoe University of Integrative analysis of epigenetic Limpopo modifications in a breast cancer cell line treated with a bioactive extract of bidens pilosa 88. H. Gomwe University of Fort Developing a model for promoting Hare physical fitness and healthy lifestyle of primary school learners in the Eastern Cape Province, South Africa 89. D.T. Goon University of Fort Training needs for the implementation Hare of the 2012 Integrated School Health Policy in the Eastern Cape Province 90. N. Gumede Mangosuthu Design, synthesis and in vitro bio- University of analytical tests of new chemical entities Technology as CYP17A1 inhibitors: targeting prostate cancer 91. T. Magoro University of Venda STAT-1 is required for the induction of interferon independent cholesterol 25-hydroxylase 92. K. Malemela University of Investigation of the probable anti- Limpopo cancer effects of the crude methanol extract of Dicerocaryum senecioides, (klotzch) j. abels, leaves on cervical HeLa cancer cells

29 93. N.D. Matume University of Venda Genetic variation within the coding region of CCR5 in chronically HIV-1 infected South African individuals 94. V. Mbombela Walter Sisulu Prevalence of obesity, hypertension University and erectile dysfunction among HIV –ve and newly diagnosed HIV +ve ART naïve patients 95. N. Mchunu University of In vitro assessment of cytochrome P450 Zululand and drug transporters modulation by polyphenolic constituents of Cyclopia genistoides 96. S. Mnwana University of Fort An intersectoral collaboration model Hare for the implementation of the integrated school health policy in the Eastern Cape Province, South Africa 97. M. Moloantoa University of Phytochemical analysis of ethyl acetate Limpopo and methanol extracts of Senna italica 98. M. Mudalahothe University of Momordica balsamina induces p53- Limpopo mediated apoptosis associated with G0/G1 cell division cycle arrest in lung A549 cancer cells 99. R. Musoliwa University of the Genetic diversity of SLCO1B1 within Western Cape indigenous South Africans and impact on enalapril therapy 100. E. Seekoe University of Fort Challenges faced by school health Hare nurses in the implementation of the 2012 Integrated School Health Policy in the Eastern Cape Province, South Africa 101. A.P. Okeyo University of Fort Evaluating the school food and Hare nutrition environment in the Eastern Cape South Africa: Implication for healthy eating of secondary school learners 102. M. Raboshakga University of The analysis of the phytochemical Limpopo profile and antioxidant activity of crude methanolic and sub-fractions of Bidens pilosa L 103. E. Seekoe University of Fort The conceptualization of the 2012 Hare Integrated School Health Policy: In the lens of principals, Life Orientation teachers, school governing bodies and ward counsellors in the Eastern Cape, South Africa

30 105. M. Tolo University of Phytochemical constituent profiles Limpopo and antioxidant activity of six different extraction formulations for analysis of Bidens pilosa L crude extract and its sub-fractions 106. T. Tshidino University of In vitro antidiabetic and cytotoxicity Limpopo properties of Commelina benghalensis acetone extract against 3T3-L1 cells

SAMRC MID-CAREER SCIENTIST PROGRAMME (MCSP) No Initials Surname University/ Research Tittle Research Unit 107. H. Adeola University of Cape Proteomic analysis of geometrically Town and ethnically classified human hair in a South African cohort 108. M. Alkelani University of Cape The role of stem cells in the Town pathogenesis of scarring alopecia 109. K. Chabaesele University of Cape Is there an association between frontal Town fibrosing alopecia and sunscreen actives? 110. E. Cloete University of Cape Interdependence between geometric, Town tensile and chemical bond behaviours of untreated curly hair fibres 111. S. Da Silva University of Cape The use of hair to detect and monitor Town hyperglycaemia – a pilot study 112. M. Gabier University of Cape The identification of novel microbial Town signatures as biomarkers in traction alopecia 114. O. Kgasha Sefako Makgatho The Stop Rheumatic Heart Disease University Through Awareness Raising, Surveillance, Advocacy, and Prevention Research Programme: Longitudinal Studies of Primary and Secondary Prevention of Rheumatic Heart Disease 115. H.A. Adeola University of Cape Differential genomic profiling for Town staging and diagnosis of traction alopecia: A pilot study 116. A. Khine Sefako Makgatho Impact of Nyaope on physical health University and organ functions 117. T. Skhakhane University of Cape Molecular approaches for Town characterisation of cicatricial alopecia

31 ABSTRACTS

SAMRC INTRAMURAL (POSTDOCTORAL) PROGRAMME

MR THOBILE MABUYA – PROGRAMME ADMINISTRATOR

32 EFFECT OF DIFFERENT FORMULATIONS OF BANANA PEEL AND GRAPE SEED IN PREVENTING OBESITY IN SPRAGUE DAWLEY RATS 1O. Aboyade, 1T. Gumata, 1D. Katerere 1 Department of Pharmaceutical Science, Tshwane University of Technology, Arcadia, Pretoria

BACKGROUND weeks. Biochemical and histopathological Worldwide, obesity has reached epidemic analyses were performed on the rats. proportions. This condition is a major contributor to the global burden of RESULTS chronic disease and disability affecting Although all the treatment groups and the many, regardless of their age, gender and negative control group had significantly race. In recent studies, the potential use higher food intake compared to the of plant products to prevent obesity has positive control group, weight gain in all been explored. these groups was significantly lower (p <0.001). The levels of triglycerides and OBJECTIVES high-density lipoprotein (HDL) observed To determine the protective effect of in all treatment groups were higher than different formulations of banana peel and those of the control group. However, grape seed on the prevention of obesity in the HDL level was only significant in Sprague Dawley rats. group 3 (p <0.05). All the treatment groups had significantly higher ALP and METHODS ALT compared to the positive control Three different formulations of banana- (p <0.001). Histopathological evidence peel and grape-seed powders were tested showed that these changes in the liver in Sprague Dawley rats for 12 weeks. The are usually associated with increased rats (n=40) were divided into five groups metabolic activity. and fed the following diets: normal diet (negative control; group 1); high- CONCLUSION fat diet (HFD; positive control; group 2); In this study, we showed that although HFD + BPGS 1 (group 3); HFD + BPGS2 these formulations prevented weight gain, (group 4) and HFD + BPGS3 (group 5). they significantly increased the triglyceride The animals were terminated after 12 and liver enzyme levels.

33 “WE TRY OUR BEST, BUT IT’S PROBABLY NOT OUR BEST”: HEALTH PROFESSIONALS’ EXPERIENCE OF PROVIDING EMERGENCY CARE TO SELF-HARM PATIENTS IN A SOUTH AFRICAN HOSPITAL 1J. Bantjes, 1A. Nel, 2K. Louw, 3I. Lewis 1 Department of Psychology, Stellenbosch University, Stellenbosch; 2 Department of Psychiatry, Stellenbosch University, Tygerberg; 3 Department of Psychiatry and Mental Health, University of Cape Town, Cape Town

BACKGROUND legally responsible for preventing suicide. Self-harm patients presenting at an Participants describe employing several emergency room (ER) are a clearly strategies to contain the anxiety of caring delineated group at elevated risk of for self-harm patients including avoiding future acts of nonfatal and fatal suicidal asking patients about current suicidal behaviour. ERs are potentially effective, ideation or intention; rigidly over-relying on albeit underutilised, sites for targeted protocols, procedures and psychometric suicide prevention interventions. scores; and shifting responsibility and “turfing” self-harm patients to psychiatry. OBJECTIVE Participants describe how the emergency In this qualitative study, we aimed to care of self-harm patients has been document the experiences of health organised into two distinct and potentially professionals tasked with providing adversarial systems – a medical system emergency medical and psychiatric care (focused on patients’ physical needs) to self-harm patients in the ER of a South and a psychiatric system (that attends to African hospital. patients’ psychosocial contexts).

METHODS CONCLUSIONS Data were collected via semi-structured Participants perceptions and the strategies interviews with 29 medical staff and they employ to contain their anxiety analysed using thematic analysis. and intolerable feelings work against adherence to evidence-based best practice RESULTS guidelines, and the provision of integrated, Providing emergency care to self-harm collaborative and person-centred care for patients is described as challenging and self-harm patients. Cartesian dualism is anxiety provoking. Factors perceived to alive and well in emergency medicine and contribute to these challenges include emergency psychiatry. The mind-body resource constraints; lack of access to split and medicine’s progression towards community-based psychosocial care; the sub- and superspecialism may potentially perception that suicide risk and intent compromise the care of self-harm patients cannot be assessed accurately; belief in ERs. that self-harm patients do not provide reliable accounts of themselves; and a perception that medical professionals are

34 THE ROLE OF CD4+ T-CELL SUBSETS IN COGNITIVE FUNCTION 1T. Bogale-Brombacher, 1K. de Gouveia, 1O. Tamgue, 1M. Scibiorek, 1F. Brombacher 1 Cape Town Component International Centre for Genetic Engineering and Biotechnology, Division of Immunology Institute of Infectious Disease and Molecular Medicine Health Science Faculty, University of Cape Town, South Africa Medical Research Council, Cape Town

BACKGROUND neurological cell populations influenced Various researchers have demonstrated by specific IL-4Rα deficiency on T cells that T cells are important for cognitive were characterised. EthoVision XT 8 functions by secreting Interleukin-4 (IL-4) was used to record data, with statistical and IL-13 during Morris water maze (MWM) analyses by ANOVA or Student t test. training. These ligands stimulate astrocytes Protocols (No. 050/015) were approved by via IL-4Receptor alpha/gamma c (IL-4Rα/ the animal ethics research committee of γc) and IL-4Rα/IL-13Rα1, respectively to the University of Cape Town, South Africa. produce brain-derived neurotrophic factor (BDNF) in the meninges to foster cognitive RESULTS functions. To better understand which T-cell subsets are important, we used a loss of function OBJECTIVES strategy by generating T-cell-specific To gain insight into the possible IL-4Ra deficient mouse models. This downstream neural mechanism mediated included Pan T-cell IL-4Ra deficient mice, by meningeal and brain parenchyma CD4+CD8- T-cell IL-4Ra deficient mice, cytokine milieu, the effect of different CD4+g/d-T-cell IL-4Ra deficient mice, cytokines and their combinations on as well as FoxP3-IL-4Ra deficient mice astrocytic expression of pro- and anti- compared to wild-type mice. Of interest, inflammatory products were examined all T-cell subsets showed reduced learning following MWM training. and memory compared to controls.

METHODS CONCLUSION For the MWM task, mice were trained MWM studies using various T-cell IL-4Ra on acquisition for four days, given four deficient mice showed impaired learning trials per day from varying entry points. and memory, suggesting that all T-cell This was followed by a single probe subsets, including regulatory T cells, trial on day five to determine effects on contribute to cognitive function. memory formation. Immunological and

35 RESUSCITATION-PROMOTING FACTORS ARE REQUIRED FOR MYCOBACTERIUM SMEGMATIS BIOFILM FORMATION 1C. Ealand, 2B. Rimal, 2J. Chang, 1L. Mashigo, 1M. Chengalroyen, 1L. Mapela, 1G. Beukes, 1E. Machowski, 2S.J. Kim, 1,3B. Kana 1 DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa; 2 Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, USA; 3 MRC- CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Centre for the AIDS Programme of Research in South Africa, CAPRISA, Durban, South Africa

BACKGROUND solid and liquid media to assess biofilm Resuscitation promoting factors (Rpfs) formation. The susceptibility to cell wall are enzymes that have previously been targeting agents was tested and proposed shown to act as growth cytokines via their alterations in PG composition were lysozyme-like activity on peptidoglycan (PG) determined using LC-MS. in the bacterial cell wall. In Mycobacterium tuberculosis, these proteins have specifically RESULTS been implicated with reactivation of latent Single and combinatorial deletion disease to its active form. Protein domain mutant strains displayed altered colony architecture reveals the presence of a morphologies and the inability to form G5 domain, previously associated with typical biofilms. Moreover, any strain bacterial biofilm formation, suggesting lacking rpfA and rpfB simultaneously that Rpfs may play an additional role in exhibited increased susceptibility mycobacterial communication. to rifampicin, vancomycin and SDS. Exogenously Rpf supplementation failed OBJECTIVE to restore biofilm formation. Relative Mycobacterium smegmatis encodes four to the wild-type, LC-MS analysis of PG distinct rpf homologues, MSMEG_5700 isolated from the strain lacking all four (rpfA), MSMEG_5439 (rpfB), MSMEG_4640 rpf genes, detected a reduced level of (rpfE2) and MSMEG_4643 (rpfE). We 4-3 cross-linked PG dimers concomitant hypothesized that strains lacking rpf genes increase of 3-3 cross-linked muropeptides. would have altered growth phenotypes. In addition, the level of PG-repeat units terminating in 1,6-anhydroMurNAc METHODS appeared to be significantly reduced. In-frame, unmarked deletion mutants (single and combinatorial) were constructed using CONCLUSION homologous recombination. Mutant strains Collectively, our data proves that Rpfs were confirmed by PCR and/or Southern play an important role in biofilm formation hybridisation. Complementation strains and antibiotic tolerance, possibly through were constructed by introducing full-length alterations in PG cross-linking and the genes downstream of native promoters at production of signalling molecules. the attB site in the chromosome. All strains, including the wild-type, were cultured on

36 HEALTH-CARE UTILISATION AND INTERNAL MIGRATION IN RURAL AND URBAN SOUTH AFRICA 1,2C. Ginsburg, 1-3M.A. Collinson, 1,2F.X. Gomez-Olive, 4M. Gross, 4M. Lurie, 4R. Wang, 1,4M.J. White 1 Medical Research Council/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2 INDEPTH Network, Accra, Ghana; 3 Department of Science and Technology/Medical Research Council, South African Population Research Infrastructure Network, South Africa; 4 Population Studies and Training Centre, Brown University, USA

BACKGROUND RESULTS Within South Africa, geographic mobility Of the Agincourt HDSS residents, 59% is high as people engage in permanent reported having utilised health services in resettlement and temporary movement. the preceding year, compared to 45% of Mobility, which results in an altered set of temporary migrant respondents. Migrants circumstances, may compromise health care were more likely to have accessed private access and continuity of care for individuals health facilities compared to rural residents requiring treatment. Not enough is known (6% of Agincourt respondents and 31% of about health-care utilisation among internal Johannesburg-based migrants who used migrants. services, attended private facilities). Logistic regression analysis revealed that female OBJECTIVE Agincourt residents were twice as likely For this paper, our objective is to explore to have used health services compared to health-care utilisation in a cohort of males, with the odds of service utilisation internal migrants and permanent residents lower for employed individuals and those originating from the Agincourt Health and with post-school education. Conversely, Demographic Surveillance System (HDSS) female temporary migrants had 0.75 times in South Africa’s rural northeast. the odds of accessing health services compared to males. METHODS A 5-year cohort study of 3800 individuals, CONCLUSIONS ages 18–40 years, commenced in 2017. Provisional results suggest that health The cohort was randomly selected from service utilisation and its determinants the Agincourt HDSS platform and includes may differ by migrant status. Information residents of the Agincourt sub-district on health service utilisation among and temporary migrants. Data have been internal migrants can assist in developing collected from 1095 Agincourt residents meaningful public health interventions that and 250 temporary migrants living in seek to improve the continuity of health Johannesburg. Descriptive statistics and care delivery across space. logistic regression models were used to examine health service utilisation and its determinants.

37 ‘WE ARE HERE FOR OUR PATIENTS’ – RESILIENCE AMIDST CHALLENGES IN PRIMARY CARE MANAGERS 1C. Brooke-Sumner, 1P. Petersen-Williams, 1B. Myers 1 Alcohol, Tobacco and Other Drug Research Unit, South African Medical Research Council, Tygerberg

BACKGROUND system, and the interpersonal interactions The South African primary health system between facility staff. Most of the faces pressure from increasing headcounts participants were women. They described a and shrinking budgets. Facility managers deep burden of care extending to patients are pivotal to service provision, interacting and particularly their staff. This linked to a directly with patients, providers and higher preference for a participatory management health structures. style that they perceived to be in conflict with health system structures. Two OBJECTIVE substantial causes of stress were commonly In this study, we investigated experiences reported, (i) seeing first-hand the adverse and challenges of primary care managers in impact of diminishing resources; and (ii) the Western Cape. facing personal accountability for facility statistics in this challenging environment. METHODS All but one remained positive of their ability In-depth interviews were conducted to address ongoing challenges. with 20 managers. NVivo 11 was used to manage data. Thematic analysis was CONCLUSIONS employed by two coders, with inductive The commitment of primary care managers constant comparative analysis to identify, positions them as a lever influencing public modify and confirm themes. health outcomes. Further investigation into the burden of care is required. Subsequent RESULTS intervention to promote mental health and Participants described navigating a support participatory management will complex workspace comprising a dynamic avoid eroding this vital human resource. relationship between the community served, the powerfully hierarchical health

38 UNMET NEED FOR CONTRACEPTION, UNPLANNED PREGNANCY AND CONTRACEPTIVE USE AMONG HIV-INFECTED AND HIV-UNINFECTED WOMEN IN SOUTH AFRICA 1W. Chirinda 1 Health Systems Research Unit, South African Medical Research Council, Cape Town

BACKGROUND RESULTS Reducing unmet needs for contraception The mean age of the sampled women and prevention of unplanned pregnancies was 26.3 years (SD 6.35), and their HIV among HIV-infected women is one of the prevalence was 31.7% (95%CI: 30.6-32.7). key components of prevention of mother- More than a third (35.5%) were unaware of to-child transmission (PMTCT) of HIV their HIV-positive status before pregnancy. strategies. Overall, 5524 (61%) reported that their pregnancies were unplanned and of these OBJECTIVE 1656 (29.4%) reported using a contraceptive We assessed unplanned pregnancies, method before pregnancy. Most (>55.4%) unmet need and contraceptive use of those using contraceptives were using among HIV-infected and HIV-uninfected injectables. Very few (<2%) were using dual postpartum women in South Africa. methods. In multivariate analysis, maternal age, marital status, knowing their partner’s METHODS HIV status, disclosure and education were Secondary data from a nationally associated with unplanned pregnancy. representative, cross-sectional survey, HIV-infected women were 2.4 times conducted in 2012/13 were analysed. Data more likely to have an unmet need for were analysed for 9277 women who self- contraception compared to HIV-uninfected reported as being HIV-positive or -negative women. Unmet need for contraception was and consented to participate in the national associated with HIV serostatus, maternal evaluation. We used a multivariable logistic age, marital status, timeliness of first regression model to estimate factors antenatal clinic visit, knowing their partner’s associated with unplanned pregnancy and HIV status, and disclosure. unmet need for contraception. CONCLUSIONS The prevalence of unplanned pregnancy and the unmet need for contraception was high in South Africa. Interventions are required to improve access to effective and reliable contraceptive methods that align with pregnancy intentions; promote dual contraception; and integration of family planning and HIV-prevention services.

39 MODELLING HIV AND ASSOCIATED FACTORS AMONG SEX WORKERS IN SOUTH AFRICA 1,2J. Coetzee, 1,3R. Jewkes, 3G. Gray 1 Gender and Health Research Unit South African Medical Research Council, Pretoria; 2 Perinatal HIV Research Unit, Division of the University of the Witwatersrand, Johannesburg, South Africa; 3Office of the President, South African Medical Research Council, Cape Town

BACKGROUND ten implementation sites in South Africa. South Africa has the highest prevalence of A minimum of one site per province will be HIV in the world, yet little is known about included. The sample size was calculated factors driving the epidemic among key based upon estimated HIV prevalence affected populations, such as sex workers and to ensure sufficient power for analysis. (SWs). In South Africa, SWs have been Participants will undergo a 40-minute, shown to have an HIV prevalence ranging interviewer-administered survey, and a from 36-89%, with 16% of HIV-positive rapid HIV test, urine toxicology test, blood female sex workers (FSWs) in Soweto sampling (STIs (all) and HIV-drug resistance having HIV-drug resistance. They are known phylogenetic testing), and a self-collection to be exposed to high levels of violence vaginal swab (STI screening). perpetrated by clients and policing officials and suffer from mental ill health. There is RESULTS no research which explains the complex We will analyse the data with STATA or SAS interconnections of these factors on HIV employing uni- and bivariate analyses. prevalence in this population to guide Descriptive data will be presented per evidence-based programming. province/site. An overall multivariate model will be developed from the national data OBJECTIVE of drivers of HIV and HIVDR among SWs To establish a national baseline prevalence using MPLUS. of HIV, HIV-drug resistance (HIVDR), adherence to antiretroviral treatment or CONCLUSIONS pre-exposure prophylaxis, violence, and Funding has been secured for data mental ill health among SWs exposed to collection to begin by Q4 2018. Milestones sex-work programmes across South Africa. and deliverables have been agreed, as has the final budget with contracts being METHODS signed. We will use a five-stage randomisation process to recruit 2000 SWs from across

40 DEPENDENT EFFECT OF PALMITATE AND SIMVASTATIN ON CELL VIABILITY AND PRODUCTION OF REACTIVE OXYGEN SPECIES USING AN IN VITRO MODEL OF DIABETIC CARDIOMYOPATHY 1,2P. Dludla, 1S. Silvestri, 1P. Orlando, 1F. Marcheggiani, 1I. Cirilli, 2R. Johnson, 2C. Muller, 2J. Louw, 1L. Tiano 1 Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy; 2 Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, South Africa

BACKGROUND were incubated with various palmitate Diabetic cardiomyopathy (DCM) is concentrations of palmitate (0.125 to 1.0 among the leading causes of death in mM) and simvastatin (0.5 to 100 µM) for diabetic patients. Patients with DCM are 24 hours. Hereafter, cell viability, cytosolic characterised by distinct cardiovascular ROS and mitochondrial superoxide radical disease (CVD)-related symptoms that production were assessed using ViaCount, include early diastolic dysfunction, which dichlorofluorescein and MitoSOX assays, may lead to hypertrophy and subsequent respectively. myocardial infarction. Oxidative stress, defined as an unbalance between RESULTS intracellular production of reactive oxygen Exposure of wild-type and NCX1- species (ROS) and antioxidant defences H9c2 cardiomyocytes showed a dose- in favour of the former, is a characteristic dependent decrease in cell viability and feature of DCM and a major cause of tissue increased production of ROS. Doses ˃ damage. Currently, there is no specific 0.5 mM for palmitate and ˃ 2.5 µM for treatment for DCM. Moreover, recent simvastatin were the most toxic for wild- evidence shows that prolonged exposure type and NCX1-H9c2 cardiomyocytes. The to statins, the widely used cholesterol- latter showed more vulnerability to high lowering agents, can worsen CVD-related palmitate and simvastatin concentrations complications through increasing oxidative when compared to wild-type cells. stress. CONCLUSION OBJECTIVES Our results indicate that hypertrophic To investigate the dose-dependent effects cardiomyocytes, representing a model of palmitate and simvastatin using an in for DCM are more vulnerable than vitro model of DCM. uncompromised cells against dyslipidaemic conditions and oxidative stress. Moreover, METHODS these effects can be worsened by An in vitro model of DCM was established prolonged exposure to statins. However, using H9c2 cardiomyocytes with altered more research is required to confirm these Na+/Ca2+ exchanger 1 (NCX1) gene. findings. Together with the wild type, which served as a control, NCX1-H9c2 cardiomyocytes

41 ISONIAZID RESISTANCE DETERMINATION: CHALLENGES IN PRACTICE 1S. Nagel, 1M. Klopper, 1A. Dippenaar, 1M. De Vos, 2C.L. Hayes, 3S. Burns, 1P.D. van Helden, 1R.M. Warren, 3J.E. Posey, 1E.M. Streicher 1 SA MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University; 2 National Health Laboratory Services; 3 Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, USA

BACKGROUND METHODS Isoniazid (INH) serves as the backbone The isolates were investigated by of combined anti-tuberculosis therapy. minimum inhibitory concentration (MIC) However, increasing numbers of determination, spoligotyping, Sanger Mycobacterium tuberculosis strains are sequencing and whole genome sequencing becoming resistant to INH through (WGS) to determine the reasons for spontaneous mutations in genomic discrepancies between the LPA and DST. regions of the bacilli, thereby threatening effectivity of treatment regimens. In South RESULTS Africa, the current diagnostic algorithm With MIC determination, spoligotyping dictates that only rifampicin resistant and Sanger sequencing, we could resolve cases are tested for INH resistance. This 16% of discrepancies. Subsequent WGS is done by the MTBDRplus line-probe of a subset of unresolved isolates revealed assay (LPA), which reports INH resistance several genomic features that may explain based on mutations in katG gene and INH resistance in the absence of canonical inhA promoter, followed by a phenotypic mutations. These include large deletions drug susceptibility test (DST) to confirm spanning the katG gene, heteroresistance INH susceptibility. However, discrepancies (mixed infections), as well as several between the results of these tests are potential novel resistance-causing frequently reported. This may result in mutations. incorrect diagnoses and the prescription CONCLUSIONS of improper drug treatment regimens. While LPA is conveniently rapid and accurate in most of the cases, phenotypic OBJECTIVES DST is necessary to detect resistance To determine the reason for discrepant conferred by less common mechanisms. LPA and DST results in 398 clinical isolates WGS can be applied to inform researchers obtained from the National Health and clinicians of such alternative resistance Laboratory Service, Port Elizabeth and to markers. These results will be used to determine the mechanism of resistance in improve current diagnostic methods for isolates where resistance is not detectable detection of INH resistance. by LPA.

42 THE POTENTIAL OF SINGLE NUCLEOTIDE POLYMORPHISMS WITHIN VIRULENCE GENES AS LINEAGE AND SUB-LINEAGE MARKERS OF MYCOBACTERIUM TUBERCULOSIS 1A. Mutshembele, 1L. Malinga, 1M. van der Walt 1 TB Platform, South African Medical Research Council, Pretoria, South Africa

BACKGROUND were compared with H37Rv. A SNP catalog Transmission of drug-resistant of virulence genes belonging to cell-wall Mycobacterium tuberculosis (M. tb) is a proteins and toxin–antitoxin system was global health problem leading to increased developed. morbidity and mortality. Traditionally, genotyping of M. tb based on molecular RESULTS finger techniques often lacks discriminatory Specific SNPs within virulence genes power in some lineages. Whole genome were associated with lineages and sub- sequencing (WGS) uses single nucleotide lineages. Seven virulence genes (higA; polymorphisms (SNPs) that have low vapC6; vapC37; vapB34; mce3B; mmaA4; levels of homoplasy and are ideally suited mce3F) with specific SNPs were associated for defining phylogenetic grouping with with lineage 2 and 4 (P<0.005). Using higA very high confidence. Genomic regions SNPs of C363T and G445T, respectively (virulence genes) within M. tb responsible differentiated strains of Beijing and S sub- for pathogenesis in the host can develop lineages with high confidence. Within SNPs for use in lineage/sub-lineage lineage 4, vapC6 differentiated strains into detection. S and X3 using G280A and T215A SNPs, respectively. Other sets of SNPs within OBJECTIVES mce3B, mmaA4 and vapC37 showed a To analyse and compare SNPs within high level of association with specific sub- virulence genes as potential markers of lineages. lineages and sub-lineages detection. CONCLUSIONS METHODS A set of detected SNPs within virulence A bioinformatics analysis of virulence genes may show the evolutionary genes from 303 WGS was performed relationship between lineages. Future from Brazil (n=2), China (n=23) and South studies needed to establish a South African Africa (n=278) downloaded from PATRIC specific M. tb SNP catalog of virulence database. Virulence genes (mazF3; genes, which will complement the WGS vapB17; vapC47; higA; vapC37; vapC38; data workflows for rapid detection of vapC6; mazF8; vapC3; mce3B; cyp125; lineage/sub-lineages. vapC25; vapB34; mce3F; vapC46; mmaA4)

43 ORAL, AIRWAY AND GUT MICROBIAL COMMUNITIES ARE ALTERED IN PATIENTS WITH ACTIVE TUBERCULOSIS 1C. Naidoo, 1G. Nyawo, 1Z. Palmer, 2Y. Li, 2B. Wu, 1G. Walzl, 1R. Warren, 2L. Segal, 1G. Theron 1 DST-NRF Centre of Excellence for Biomedical Tuberculosis Research and South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa; 2 New York University School of Medicine, NY, USA

BACKGROUND RESULTS Tuberculosis (TB) is the leading infectious In BAR-TB, cases were enriched with cause of death globally, however, its anaerobes, Paludibacter and Prevotella association with the microbiome is poorly in oral washes and sputum, and had a understood. diverse gut microbiota (Shannon’s diversity; p=0.025 vs. healthy controls) dominated by OBJECTIVES butyrate producers, Lachnospiraceae and To test this association, saliva, sputum and Blautia. Cases were significantly depleted stool specimens were collected from two of health-promoting Bifidobacterium ongoing randomised controlled trials, BAR- compared to healthy controls in the stool TB and NExT. specimens. Metabolic pathways encoding short-chain fatty acid production were METHODS enriched in cases. In NExT, patients in the In BAR-TB, 106 pre-treatment patients with intervention arm, but not the routine arm, presumptive TB were recruited, where cases had reduced diversity and altered microbial and symptomatic controls were classified composition by 6-weeks of MDR treatment, based on a positive (n=58) or negative compared to pre-treatment. These effects (n=47) Mycobacterium tuberculosis culture. are likely mediated by linezolid, a broad- Patients in NExT had multidrug-resistant spectrum antibiotic in the intervention arm. (MDR)-TB and were randomised to a 24-month routine arm (n=4) or a 6-month, CONCLUSIONS injection-free intervention arm (n=5). The gut microbiota of TB cases is Up to two healthy household contacts significantly perturbed at pre-treatment. (confirmed culture- or Xpert-negative) per Different regimens likely differentially patient had the same specimens collected disrupt the microbiome, however, the (n=155 in BAR; n=15 in NExT). 16S rRNA long-term significance (e.g. role in relapse, sequencing was done using the Illumina post-TB complications) requires further MiSeq. Operational taxonomic units investigation. Future analyses will explore were assigned to sequences using QIIME the association of microbiota-derived and Greengenes, and statistical analyses metabolites with immune markers related done in R. LEfSe was used for biomarker to TB. discovery and PICRUSt used for inference of microbial functional content.

44 PROTEOMIC ANALYSIS REVEALS THAT SULFAMETHOXAZOLE INDUCES OXIDATIVE STRESS IN M. TUBERCULOSIS 1A.H. Ngwane, 1R. Sarkar, 1C. Mdladla, 1L. Macingwana, 1R-D. Pietersen, 1D.L. Tabb, 1P.D. van Helden, 1I. Wiid, 1B. Baker 1 DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa

BACKGROUND than two in either direction and the The primary target of sulfamethoxazole corresponding q-value from false discovery (SMX) is folP1 (folate synthesis) in rate-adjusted ANOVA was less than or mycobacteria; however, SMX may affect equal to 0.05. other secondary targets in M. tuberculosis. We investigated the potential additional RESULTS targets of SMX in a clinical isolate of M. We identified approximately 1500 tuberculosis. proteins of which 46 were differentially regulated through proteomic analysis. OBJECTIVES These included 25 upregulated and 21 To explore the proteomics profile of M. downregulated proteins. The oxidative tuberculosis treated with SMX at sub-lethal stress-related proteins (Rv2428, ahpC; concentration and evaluate downstream Rv2394, ggtB) and an enzyme from the effects other than the primary target. electron transport chain (ndh-II, Rv1854c) were found to be upregulated. We also METHODS observed downregulation of deazaflavin- The (MGIT) BACTEC 960 system was used dependent nitroreductase (Rv1558, ddn) for activity and MIC99 determination for all and upregulation of two efflux pump- M. tuberculosis strains received from our associated membrane transporters (Rv2936 strain bank. Orbitrap mass spectrometry drrA, Rv1232 Mg-transporter) in response was used to determine the identities to SMX treatment. Our gene expression of differentially expressed proteins in a analysis correlated with the observed clinical strain of M. tuberculosis following proteomic changes. We investigated the treatment with a sub-lethal concentration anti-folate activity of SMX and oxidative of SMX for two hours. The gene expression stress generation. of selected differentially expressed proteins was investigated by qPCR. Based on three CONCLUSION biological replicates per condition, a fold SMX may affect various other change (SMX treatment vs. control) and regulatory pathways at a proteomic a p-value (ANOVA) were calculated for and transcriptomic level which could be each protein. A protein was considered considered as additional targets of SMX in “regulated” if its fold change was greater M. tuberculosis.

45 NANOFORMULATION OF ARTEMISIA AFRA AND ITS POTENTIAL BIOMEDICAL APPLICATIONS IN TYPE 2 DIABETES 1B. Pearce, 1N. Liebenberg 1 Precision Medicine Unit, Department of Biotechnology, Faculty of Natural Science, University of the Western Cape

BACKGROUND OBJECTIVES Current research classifies type 2 diabetes To produce encapsulated gold nanoparticles as one of the most prevalent non- from A. afra, by phytosynthesis, and communicable diseases in South Africa. determine their effect on glucose uptake in Approximately 285 million people are hepatocytes in vitro as an alternative and affected globally with an expected increase additive to metformin in non-respondent to 595 million by the year 2035. Metformin, patients. a first-line drug in the treatment of type 2 diabetes, has been shown to have an METHODS efficacy rate of 43% attributable to poor An in vitro evaluation was conducted by drug uptake and metabolism. performing plant extractions from the mentioned species. Gold nanoparticles, Furthermore, herbs commonly used as encapsulated by the plant extract, were traditional medicine have shown promise in produced and their effect on glucose the treatment of type 2 diabetes. Artemisia uptake determined. afra, also known as African Wormwood, RESULTS is one of the most widely used herbs in Bioassay-guided characterisation of traditional medicine. This specific species the plant extract was conducted to has been extensively studied and is identify active phytochemicals. Individual believed to affect glucose uptake as well phytochemicals were used to produce as insulin productivity in the body. Drug varying sizes of gold nanoparticles, capped delivery and uptake systems are important solely by identified active agents. aspects of precision medicine, the science of ensuring medication works optimally CONCLUSION for each one, as they may bypass genetic Gold nanoformulations produced from the factors and provide optimal efficacy of active phytochemicals will be evaluated these treatments. for altered glucose uptake alongside metformin treatment in hepatocytes.

46 NOVEL QPCR ASSAYS FOR THE MEASUREMENT OF IMMUNE GENE EXPRESSION IN AFRICAN LION (PANTHERA LEO) WHOLE BLOOD 1T. Sylvester, 1A.G. Loxton, 1P.D. van Helden, 1M.A. Miller, 1S.D.C. Parsons 1 SAMRC Centre for TB Research; DST/NRF Centre of Excellence for Biomedical Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa

BACKGROUND GATA3, TBX21, CD4, FCGR1A, CCL2, African lions (Panthera leo) influence CXCL11 and TNFA mRNA of African lions the ecosystem function and biodiversity by qPCR. The amplification efficiencies and infectious pathogens such as of all assays were similar, which allowed Mycobacterium bovis and feline the determination of gene expression immunodeficiency virus (FIV) and may in relation to that of the reference gene impact the ecology of this species. To YWHAZ. better understand how these pathogens affect lion populations, biomarkers that RESULTS act as indicators of disease states are All assays were able to amplify mRNA required. In humans, the measurement from whole blood samples of four selected of gene expression is a valuable indicator African lions with varying states of M. bovis of immune status and this approach has and FIV infection. previously been used to detect M. bovis CONCLUSION infection in lions. The assays developed in this study provide tools for the measurement of immune gene OBJECTIVES expression in African lions and could be To determine mRNA sequences of selected used to investigate disease states in this lion gene transcripts and use these to species. design and optimise qPCR assays for the measurement of gene expression in lion whole blood.

METHODS Novel primer sets were designed to measure the expression of CXCL8, IL10,

47 EFFECTS OF ROOIBOS PHENOLIC COMPOUNDS ON MICROBIOTA REGULATION AND PREVENTION OF THE METABOLIC SYNDROME 1N. Thovhogi, 1K. Gabuza, 1J. Louw, 2M. Tobin, 2P. Mobo, 2R. Mundembe 1 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg; 2 Biotechnology Department, Faculty of Applied Science, Cape Peninsula University of Technology

BACKGROUND Primate Unit, with access to water ad lib via Development of metabolic diseases is an automatic watering device. Treatment accompanied by changes in gut microbiota consisted of a food bolus containing an phenotype, including a decrease of aspalathin-enriched unfermented rooibos beneficial bacterium and increase of extract, administered three times daily pernicious bacteria. Increasing evidence for 42 days. Baseline blood and faecal strongly supports that development of type sampling were performed for biochemical, 2 diabetes (T2D) is closely associated with inflammatory and immunological cytokine gut microbiota. An unhealthy diet rich in determinations. saturated fats and refined carbohydrates, along with sedentary lifestyle is associated RESULTS with increased risk of developing metabolic The components of gut microbiota from diseases including obesity and T2D. these monkeys were examined to determine Obesity represents a state of chronic the effects of rooibos extract on microbiota, inflammation characterised by increased and the shifts in gut bacterial communities levels of proinflammatory cytokines and were determined by 16S ribosomal RNA chemokines resulting in pathological gene sequencing. Preliminary results changes in insulin-sensitive tissues and indicated that treating the anaerobic faecal β-cells. Recent research indicated that cultures with polyphenols, modulated gut microbiota plays a crucial role in the growth of bacterial species related to maintaining health or promoting conditions the diet and metabolic diseases. These such as obesity and diabetes. monkeys’ diet has been associated with gut microbiota diversity. OBJECTIVES To define the role of rooibos polyphenols CONCLUSION in the beneficial gut microbiota and their Studying the bioactivity of rooibos effect on biochemical and inflammation flavonoids and microbial degradation parameters in monkey models of obesity products would give greater insight into and pre-diabetes, respectively. their respective beneficial roles in the metabolism and maintenance of health. METHODS The monkeys on high fat diabetogenic diet were selected and maintained at the SAMRC

48 SAMRC CLINICIAN RESEARCHER DEVELOPMENT (MD.PHD) PROGRAMME

MR THOBILE MABUYA – PROGRAMME ADMINISTRATOR

49 A 12-WEEK EXERCISE INTERVENTION IMPROVES INSULIN SENSITIVITY IN SEDENTARY BLACK OBESE SOUTH AFRICAN WOMEN: THE ROLE OF ECTOPIC LIPID CONTENT 1M. Fortuin-de Smidt, 1,2A.E. Mendham, 1L. Clamp, 3A. Alhamud, 4J. Hauksson, 5T. Olsson, 1,2J.H. Goedecke 1 Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town (UCT), Cape Town, South Africa (SA); 2 Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, S; 3 Department of Human Biology, MRC/ UCT Medical Imaging Research Unit, UCT, Cape Town, S; 4 Department of Radiation Sciences, Umeå University Hospital, Umeå, Sweden; 5 Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden

BACKGROUND peak oxygen consumption, SI (frequently Black South African (SAn) women have sampled intravenous glucose tolerance a high prevalence of obesity and insulin test) and ectopic lipid content of liver, resistance (IR). Ectopic lipid deposition has pancreas and skeletal muscle (magnetic been linked to IR and type 2 diabetes (T2D). resonance spectroscopy). Exercise training is used to prevent and or manage obesity and T2D. However, the RESULTS effect of exercise on pancreatic and skeletal The exercise and control groups were muscle lipid content is inconclusive. similar at baseline. The exercise group experienced an improvement in SI (median OBJECTIVES (IQR): 2.0 (1.2-2.8) to 2.2 (1.5-3.7) (mU/l)- To evaluate the effect of exercise training 1min-1) with no change in the control group on insulin sensitivity (SI) and secretion (group*time p=0.037). Pancreatic lipid and to determine whether any changes content decreased in the exercise group were associated with changes in body (8.9% (3.6-24.8) to 6.8% (2.3-11.8)) with no composition, body fat distribution and change in the control group (group*time ectopic fat deposition. p=0.007). Only in the exercise group, the improvement in SI was associated with a METHODS decrease in hepatic lipid content (β -0.03, Obese black SAn women (mean age 23 ± p=0.038) but not with changes in pancreatic 3.5 years) were randomly assigned to an and skeletal muscle lipid content. exercise (n=23) or control (n=22) group. The exercise group completed 12 weeks CONCLUSION of aerobic and resistance exercises; the Hepatic lipid content played a role in the control group was advised not to change improvement of insulin sensitivity after an their physical activity. Pre- and post- exercise programme in black obese SAn intervention testing included assessment of women.

50 ADOLESCENTS ON ANTIRETROVIRAL THERAPY IN CAPE TOWN, SOUTH AFRICA 1L. Githinji, 1D. Gray, 1S. Hlengwa, 1T. Machemedze, 1H.J. Zar 1 Department of Paediatrics and Child Health, Red Cross Children’s Hospital and MRC Unit on Child and Adolescent Health, University of Cape Town, South Africa

BACKGROUND 3.3) log copies. HIV-infected adolescents Chronic lung disease is common in had lower lung function compared to perinatally HIV-infected adolescents. uninfected at both time points, p<0.05. There is little data on the lung function Obstructive or mixed pattern spirometry progression in HIV-infected adolescents on was more common in HIV-infected antiretroviral therapy (ART). adolescents (p<0.05), with no difference in reversibility between HIV-infected and OBJECTIVE -uninfected groups, p>0.05. Previous To investigate the progression of lung pulmonary tuberculosis or lower respiratory function over two years in HIV-infected tract infection was associated with lower adolescents in the Cape Town Adolescent lung function, p<0.01 for both. Antiretroviral cohort (CTAAC). CONCLUSIONS METHODS HIV-infected adolescents had lower lung HIV-infected adolescents, 9–14 years, function and more obstructive or mixed on ART, underwent spirometry with spirometric patterns than uninfected lung bronchodilator testing at enrolment and function tracked over time. In this study, we two years later. Healthy HIV-uninfected, highlight the importance of strategies to matched controls were also tested. Linear optimise lung function early in HIV-infected mixed models were used to compute children. longitudinal changes in lung function.

RESULTS Of the adolescents tested at baseline and at 24 months, 428 were HIV-infected and 90 HIV-uninfected. Their mean enrolment (SD) age was 12.0 (1.6) years, with 50.4% males, and median (IQR) viral load 2.2 (1.6-

51 THE RELIABILITY OF ESTIMATED GLOMERULAR FILTRATION RATE IN SOUTH AFRICAN CHILDREN 1J. Holness, 2A. Brink, 3M.R. Davids, 1J. Warwick

1 Division of Nuclear Medicine, Stellenbosch University and Tygerberg Hospital, Cape Town; 2 Department of Paediatrics, Division of Nuclear Medicine, University of Cape Town and Red Cross War Memorial Children’s Hospital, Cape Town; 3 Division of Nephrology, Stellenbosch University and Tygerberg Hospital, Cape Town

BACKGROUND the plasma clearance of Cr-51 EDTA Accurate measurement of kidney function using the slope-intercept method. GFR is essential in a subgroup of children with was estimated (eGFR) from a same-day chronic kidney disease and those being serum creatinine sample using the new treated with nephrotoxic drugs. Glomerular bedside Schwartz formula, Gao’s quadratic filtration rate (GFR) is widely accepted as equation, and the full age spectrum (FAS) the best measure of kidney function, yet it is equation. The bias, precision and accuracy seldom measured in children. In most cases, of each equation were determined, and GFR is estimated using a creatinine-based the agreement between eGFR and mGFR equation. However, these equations were determined using Bland-Altman analyses. all developed in predominantly Caucasian populations in North America and Europe. RESULTS Thus far, they have not been validated in A total of 173 were included (100 female; African children. Because of differences in median age 9 years; median GFR 91.5 2 pathology and socio-economic conditions, ml/min/1.73m ). The correlation between it is hypothesised that serum creatinine eGFR and mGFR was poor (r2=0.40-0.45). levels will be lower on average leading to All equations over-estimated GFR with 2 higher GFR estimates. median biases of 16.0-26.8 ml/min/1.73m . RMSE values ranged between 14.8 and OBJECTIVE 34.8 ml/min/1.73m2. The accuracy (P30 To determine the reliability of estimated values) ranged between 43% and 63%. GFR in South African children. CONCLUSIONS METHODS Estimated GFR cannot replace measured A cross-sectional study on children referred GFR in South African paediatric patients for GFR measurement at the Red Cross because of extremely poor accuracy. There Children’s Hospital, Cape Town, took place is a need for developing an equation from between February 2014 and November local data as well as increased availability of 2017. GFR was measured (mGFR) from GFR measurement.

52 THE INTRODUCTION OF VIOLENCE AND INJURY OBSERVATORIES SUGGESTS A REDUCTION IN VIOLENCE-RELATED INJURY IN ADULT POPULATIONS. A SYSTEMATIC REVIEW AND META-ANALYSIS 1A. Jabar, 1F. Fong, 1D. Barth, 2M. Chavira, 3M.T. Cerqueira, 1R. Matzopoulos, 1M. Engel 1 School of Public Health and Family Medicine, Health Sciences Faculty, University of Cape Town, 2 College of Health Sciences, University of Texas, El Paso, 3 United States–Mexico Border Office, Pan American Health Organization

BACKGROUND English language empirical studies, three The introduction of integrated violence Spanish and one Portuguese technical and injury observatories (VIO) at local and reports met our inclusion criteria. Studies regional level is promoted for preventing were conducted in the United Kingdom crime and violence. Key strategies to (n=3), Colombia (n=2), Brazil (n=1) and achieve this end include maximising inter- Uruguay (n=1). Meta-analysis of these institutional cooperation, information- studies suggested a 29% reduction in sharing between stakeholders, timely data violence-related injury in adult populations analysis and, security policy development following the introduction of a violence and initiatives to enhance governance. injury observatory (RR=0.79; 95% CI, 0.49 to 1.01). Results from technical reports as OBJECTIVE a sub-group showed improvement over To summarise the results from existing those from empirical studies (RR=0.58; 95% studies reporting on the effectiveness of CI, 0.26 to 1.30) versus (RR=0.92; 95%CI, the introduction of violence and injury 0.42 to 2.00). Several potentially eligible observatories. studies were excluded because of study- design limitations including poorly-defined METHODS outcomes, lack of controls or baseline data, We searched several databases, or inadequate sampling. supplemented by searches in grey literature including technical reports. Searches CONCLUSIONS comprised studies from January 1990 to This systematic review provides October 2017. Study quality was assessed evidence suggesting the effectiveness using a validated quality assessment of the introduction of violence and injury tool. Disagreements were resolved by observatories and surveillance systems consensus among three authors. This as an intervention to reduce violence in review protocol has been published in adult populations. This review may serve PROSPERO International Prospective as a template for evaluative research in Register of systematic reviews, registration violence and injury observatories and in number 2014:CRD42014009818. other applications, such as health-related observatories aimed at producing social RESULTS change. Of 3105 potentially relevant unique citations from all literature searches, three

53 THE DECENTRALISED DRUG-RESISTANT TB PROGRAMME IN SOUTH AFRICA: FROM POLICY TO IMPLEMENTATION 1W. Jassat, 1H. Schneider, 2M. Moshabela 1 School of Public Health, University of the Western Cape; 2 School of Nursing and Public Health, University of KwaZulu-Natal

BACKGROUND implementation in two provinces. In the A policy supporting decentralised drug- case study, we will explore the components resistant (DR)-TB treatment provision, of the policy triangle to generate a refined was introduced in 2011, but thus far, theory of DR-TB policy implementation implementation has been suboptimal. relevant to the South African context. Data With adequate investment in health, why collection will combine qualitative and does good policy fail to be implemented quantitative methods, including routine well in South Africa? Drawing on the Policy data analysis, document review, in-depth Triangle framework, it is theorised that interviews and observation. A cross- content, actors and processes of policy case comparison of the individual case interact in context-specific ways to inform descriptions will be followed by a process implementation. A better understanding of analytic generalisation. of these implementation dynamics will contribute lessons for strengthening future RESULTS implementation of DR-TB policy. I will present preliminary work including (a) a review of implementation frameworks OBJECTIVES and theories from different disciplinary To explore the implementation of the perspectives; (b) process analysis (timeline) decentralised DR-TB programme in South of DR-TB implementation in South Africa; Africa, and specific factors explaining and (c) a review of DR-TB financing. differences in access to and quality of services in two provinces, Western Cape CONCLUSION and KwaZulu-Natal. Through this study, we anticipate providing recommendations to improve the DR-TB METHODS programme and contribute to the field This study design will be a comparative case of policy analysis and implementation study of the DR-TB decentralisation policy research in general.

54 PERCUTANEOUS PERICARDIOSCOPY IN A POPULATION WITH A HIGH PREVALENCE OF TUBERCULOUS PERICARDITIS – IMPROVING THE DIAGNOSTIC YIELD AND ADVANCING THE TIME TO DIAGNOSIS 1C. Kyriakakis 1 Division of Cardiology, Stellenbosch University and Tygerberg Hospital

BACKGROUND RESULTS Establishing a definite diagnosis of A hundred patients of which 59 males tuberculous (TB) pericarditis via direct participated, their mean age was 37.9 ± detection of Mycobacterium tuberculosis 13.5 years, and 60 were HIV infected (mean (MTB) is challenging and not always CD4=192.7 cells/µL). A pericardial biopsy possible using conventional investigations. could be obtained in 82 participants, and Previous studies have demonstrated a low 54 (65,8%) of these had definite pericardial yield using either direct microscopy or TB. The yield by examining pericardial tissue mycobacterial culture on pericardial fluid was significantly higher than by examining alone. pericardial fluid (96,3% (52/54) vs. 72,2% (39/54); p<0.05). 34 tissue samples were OBJECTIVE positive by smear and/or histology (11 AFB We evaluated the potential advantage positive, 12 had granulomas, and 11 had of minimally invasive percutaneous both), while 15 tissue samples were only pericardioscopic biopsy of the pericardium culture-positive. Of the 39 culture-positive in the diagnosis of TB pericarditis. fluid samples, ten were smear-positive.

METHODS CONCLUSIONS Patients presenting with a moderate-to- Histological and microbiological large pericardial effusion were offered examination of pericardial tissue resulted pericardiocentesis via a standard procedure, in a significantly higher yield than an followed by percutaneous pericardioscopy examination of pericardial fluid, with 15 of and pericardial biopsy. Pericardial fluid the 54 confirmed cases (27,7%) identified evaluation included biochemistry, cell only on examination of pericardial tissue. count, smear microscopy and TB culture. In contrast to the assessment of pericardial Pericardial biopsy specimens underwent fluid where a definite diagnosis of TB was direct smear microscopy for acid-fast mainly dependent on culture, pericardial bacilli (AFB), TB culture and histological biopsy enabled a more rapid diagnosis by examination. Definite TB pericarditis was microscopy or histology. defined as at least one specimen positive for AFB, MTB culture, or presence of granulomas on histology.

55 POSTNATAL MOOD AND SOCIO-ECONOMIC CONTEXT AMONG LOW- INCOME WOMEN IN JOHANNESBURG, SOUTH AFRICA 1C. Marsay, 2L. Manderson, 1U. Subramaney 1 Department of Psychiatry, University of the Witwatersrand, Johannesburg; 2 School of Public Health, University of the Witwatersrand, Johannesburg

BACKGROUND women who were recruited from a high-risk Maternal depression is a significant public antenatal clinic in Johannesburg. health problem affecting proportionally more women living in low- and middle- RESULTS income countries such as South Africa than Women’s experiences were common women in high-income countries. Maternal whether or not they had a diagnosis depression has multiple aetiologies, of postnatal anxiety or depression, and social and environmental factors and reflected the social and economic are important contributing factors and circumstances in which they lived. determinants of risk. Promotion of mental health through action on the social determinants of health is OBJECTIVES needed, with an emphasis on poverty In this article, we explore the experiences alleviation, secure employment and of low-income, urban women living in enhancing already existing social support Johannesburg, who underwent antenatal structures such as churches and extended screening for anxiety and depression and family. have since given birth. We were interested to find out how their mood changed or CONCLUSION remained the same postnatally, and to Social and political strategies can play an identify specific contextual factors that important role in mitigating the effects of might have influenced these changes. postnatal depression and addressing its underlying causes for women and their METHODS families in South Africa. We conducted focused ethnographic interviews using informal deductive conversational methods with 20 postnatal

56 IMPACT OF IMPLEMENTATION OF GENE XPERT ULTRA ON TB DIAGNOSIS IN SOUTH AFRICA 1H. Moultrie, 2S. Candy, 3A. van Rie, 2N. Ismail 1 Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, School of Pathology, University of the Witwatersrand, South Africa; 2 Centre for Tuberculosis, National Institute for Communicable Diseases, Division of National Health Laboratory Service, Sandringham, Johannesburg, South Africa; 3 Department of Epidemiology and Social Medicine, University of Antwerp, Antwerp, Belgium

BACKGROUND regression methods were utilised to assess The Gene Xpert Ultra TB test was the gradual effects of the introduction of implemented in South Africa between Ultra Xpert. The primary a priori impact October 2017 and June 2018, with Ultra model specified a gradual slope change in tests comprising >50% of all Xpert tests by the TB positivity rate during the period of January 2018. The sensitivity of Xpert Ultra Ultra rollout. is 2.2-7.6% higher (depending on smear negativity rates), and specificity 0.7% lower, RESULTS than Xpert MTB/RIF. We modelled the The number of patients tested for TB, and effects of Xpert Ultra on TB positivity rates Xpert+ TB cases both demonstrated long- and estimated the additional number of TB term declining trends with seasonal peaks cases diagnosed. during the winter cough season. In contrast, the TB positivity rate was stable with METHODS seasonal peaks during the December and Monthly Xpert MTB/RIF and ULTRA test January months. The Xpert positivity rate data were extracted from the NHLS ratio for Ultra in the final selected model Corporate Date Warehouse between was 1.10 (95%CI: 1.05 – 1.16). Xpert Ultra July 2014 to June 2018. Xpert testing implementation resulted in an additional data were de-duplicated. TB positivity 8,600 (95%CI: 2,400 – 14,700) TB cases rates were analysed using negative being diagnosed between October 2017 binomial regression models that allowed and June 2018 in South Africa. for over-dispersion, incorporated Fourier transformations of time to account for CONCLUSION seasonality and included an indicator The implementation of Xpert Ultra variable for Ultra. Standard time-series increased the TB Xpert positivity rate and diagnosed an additional 8,600 cases.

57 PLASMA KAPOSI’S SARCOMA HERPESVIRUS DNA AS A PROGNOSTIC BIOMARKER 1F. S haik, 1A. Mosam, 2T.S. Uldrick 1 Department of Dermatology, University of KwaZulu-Natal, Durban, South Africa; 2 Global Oncology, Fred Hutchinson Cancer Research Center, Seattle, WA

BACKGROUND instructions. Quantification of KSHV DNA Kaposi’s sarcoma herpesvirus (KSHV) is the will be determined by real-time polymerase causative agent of Kaposi sarcoma (KS). chain reaction amplification of a conserved Sub-Saharan Africa is burdened with the region of the open-reading frame (ORF) highest seroprevalence of KSHV infection 26 minor capsid gene. Statistical analysis with estimates ranging from 20–45% in will be conducted using SPSS with p<0.05 South African adults. KSHV seropositivity considered statistically significant. Non- is associated with HIV, which markedly parametric testing will be used and results increases the risk of KSHV-associated represented as medians. malignancies and KS remains the commonest cancer in HIV-infected patients RESULTS in sub-Saharan Africa. Pre-treatment analysis of KSHV seroreactivity and plasma KSHV VL will OBJECTIVE be conducted in 112, ART-naïve South To evaluate the relationship between African patients with biopsy-confirmed KSHV-seropositivity and viral load (VL) with HIV-associated KS; 50 men and 62 women immunological and clinical KS parameters. followed up prospectively over 12 months.

METHODS CONCLUSIONS KSHV seroreactivity and VL will be correlated In this study, we will demonstrate any with HIV VL and CD4 counts. KSHV VL associations between KSHV seropositivity will also be evaluated as a marker for KS and VL with immunological as well as staging (using ACTG criteria) and to predict clinical parameters. Pre-treatment KSHV clinical KS response (graded as complete, VL may predict KS disease progression and partial, stable and progressive disease therefore considered as a marker to identify using ACTG criteria). DNA will be extracted those patients who may benefit from more and purified with the QIAamp Blood Kit aggressive treatment. (Qiagen) according to the manufacturer’s

58 HAIR CORTISOL LEVELS IN POSTTRAUMATIC STRESS DISORDER PATIENTS VERSUS CONTROLS 1L. van den Heuvel, 2T. Stalder, 3C. Kirschbaum, 1S. Seedat 1 Department of Psychiatry, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa; 2 Clinical Psychology, University of Siegen, Siegen, Germany; 3 Biological Psychology, TU Dresden, Dresden, Germany

BACKGROUND status and severity scores in 328 females of Hair cortisol levels can provide insights mixed ancestry. Hair samples, representing into longer-term hypothalamic pituitary a three-month retrospective window adrenal (HPA) axis function, thus providing of cortisol levels, were obtained from a possible biomarker of chronic stress. cases and controls and analysed with Posttraumatic stress disorder (PTSD) is liquid chromatography-tandem mass a disorder characterised by a sustained spectrometry. maladaptive response that develops following exposure to life-threatening RESULTS traumatic events. Hair cortisol levels may Hair cortisol levels were significantly higher provide insight into the role of a persistently (p < 0.001) in 167 patients with PTSD than in dysregulated endocrine-mediated stress 161 trauma-exposed controls. Hair cortisol response in PTSD. levels further correlated with overall PTSD severity (rs = 0.22, p < 0.001) as well as the OBJECTIVES severity of PTSD symptoms on all symptom We aimed to determine whether hair domains in the sample overall. cortisol levels were associated with PTSD diagnostic status and severity in SHARED CONCLUSIONS ROOTS study participants using a case- These findings demonstrate an increase in control design. SHARED ROOTS evaluated long-term cortisol levels in patients with pathogenetic factors that contribute to PTSD, that can be differentiated by trauma increased risk for cardiovascular disease, as exposure per se, with a clear dose-response defined by the metabolic syndrome (MetS), relationship that provides evidence of a in neuropsychiatric disorders. chronically dysregulated neuroendocrine- mediated stress response in PTSD. The METHODS association of elevated cortisol levels with We administered the Clinician- metabolic markers in patients with PTSD Administered PTSD Scale for DSM-5 requires further interrogation. (CAPS-5) to determine PTSD diagnostic

59 HAIR CORTISOL LEVELS IN POSTTRAUMATIC STRESS DISORDER PATIENTS VERSUS CONTROLS 1L. van den Heuvel, 2T. Stalder, 3C. Kirschbaum, 1S. Seedat 1 Department of Psychiatry, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, South Africa; 2 Clinical Psychology, University of Siegen, Siegen, Germany; 3 Biological Psychology, TU Dresden, Dresden, Germany

BACKGROUND status and severity scores in 328 females of Hair cortisol levels can provide insights mixed ancestry. Hair samples, representing into longer-term hypothalamic pituitary a three-month retrospective window adrenal (HPA) axis function, thus providing of cortisol levels, were obtained from a possible biomarker of chronic stress. cases and controls and analysed with Posttraumatic stress disorder (PTSD) is liquid chromatography-tandem mass a disorder characterised by a sustained spectrometry. maladaptive response that develops following exposure to life-threatening RESULTS traumatic events. Hair cortisol levels may Hair cortisol levels were significantly higher provide insight into the role of a persistently (p < 0.001) in 167 patients with PTSD than in dysregulated endocrine-mediated stress 161 trauma-exposed controls. Hair cortisol response in PTSD. levels further correlated with overall PTSD severity (rs = 0.22, p < 0.001) as well as the OBJECTIVES severity of PTSD symptoms on all symptom We aimed to determine whether hair domains in the sample overall. cortisol levels were associated with PTSD diagnostic status and severity in SHARED CONCLUSIONS ROOTS study participants using a case- These findings demonstrate an increase in control design. SHARED ROOTS evaluated long-term cortisol levels in patients with pathogenetic factors that contribute to PTSD, that can be differentiated by trauma increased risk for cardiovascular disease, as exposure per se, with a clear dose-response defined by the metabolic syndrome (MetS), relationship that provides evidence of a in neuropsychiatric disorders. chronically dysregulated neuroendocrine- mediated stress response in PTSD. The METHODS association of elevated cortisol levels with We administered the Clinician- metabolic markers in patients with PTSD Administered PTSD Scale for DSM-5 requires further interrogation. (CAPS-5) to determine PTSD diagnostic

60 A PROSPECTIVE STUDY OF THE EPIDEMIOLOGY OF SEVERE CUTANEOUS ADVERSE DRUG REACTIONS AND ASSOCIATED NEUROPSYCHIATRIC SEQUELAE 1E. Zitha, 1R.J. Lehloenya, 2P. Naude, 3J. Peter, 4D. Stein 1 Division of Dermatology, Department of Medicine, University of Cape Town (UCT) & Groote Schuur Hospital; 2 Department: Psychiatry & Mental Health, Co-head of the Division of Translational Neuropsychiatry, UCT; 3 Division of Immunology & Allergology, UCT and Groote Schuur Hospital; 4 Head of the Department of Psychiatry & Mental Health and the Division of Psychopharmacology & Biological Psychiatry, UCT & Groote Schuur Hospital

BACKGROUND METHODS There are limited data on the epidemiology We will conduct a prospective cohort of depression in epidermal necrolysis study of EN patients with sex-, and an HIV- (EN). Post-EN depression seems higher, a status-matched comparison group at three contextually novel finding that was limited time-points to assess for depression using by the challenges of studying rare diseases, validated tools. We will conduct multiplex viz. small cohorts, lack of ideal control bead assays of interleukin (IL)-6, interferon- groups, and observer bias. Furthermore, alpha (IFN-α) and tumour necrosis no direct association between EN and factor alpha (TNF-α), enzyme-linked depression was adequately established. immunosorbent assay (ELISA) kit (Arbor Consequently, we want to improve on Assays) of hair cortisol levels. Linear-mixed these data and conduct a mechanistic models will be used to describe the clinical study to uncover the possible correlation and laboratory features as outcomes. Data between EN and depression. analysis will be conducted using Stata 15 (StataCorp, College Station, Texas, USA). OBJECTIVES To determine the risk factors for the RESULTS development of depression following EN We are currently addressing the concerns in Cape Town; establish a database (Afro- raised by the Human Research Ethics SCARLI registry) of EN in Cape Town, South Community at UCT (HREC/REF: 083/2018) Africa; determine the incidence, prevalence for final ethical approval. and evolution of depression in EN in Cape Town; describe the differences in the levels CONCLUSION of pro-inflammatory cytokines (IL-6, αIFN- Will be based on the findings of the study. and TNF-α) in depressed patients with EN; and to show that hair cortisol levels in the period preceding EN, predict depression.

61 SAMRC INTERNSHIP SCHOLARSHIP PROGRAMME (ISP)

MS JORENE NAIDOO – PROGRAM ADMINISTRATOR

SAMRC INTERNSHIP SCHOLARSHIP PROGRAMME (ISP)

MS JORENE NAIDOO – PROGRAMME ADMINISTRATOR

62 GENETIC POLYMORPHISMS AND IN VITRO ANALYSIS OF SLC22A2 AND SLC47A2 PROMOTERS IN THE XHOSA POPULATION 1Z. Abrahams-October, 1M. Benjeddou, 2R. Johnson 1 Precision Medicine Unit, Science Faculty, University of the Western Cape, Bellville; 2 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa

BACKGROUND METHODS Membrane transporter genes are DNA was extracted from buccal swabs responsible for the absorption, distribution using a standard salt lysis method. The and excretion of various endogenous promoter regions of the selected genes and exogenous substrates. Genetic were sequenced to identify the various polymorphisms within transport genes haplotypes present in the population. contribute to the variation in drug response Samples representative of the haplotypes among individuals. In previous studies, identified were cloned into a promoter-less many single nucleotide polymorphisms vector and promoter activity was measured (SNPs) within the promoter and exonic by the expression of Luciferase. regions of genes have been indicated within the solute carrier (SLC) superfamily RESULTS exhibit variation for metformin transport. Seven SNPs, i.e. rs150063153, rs59695691, Polymorphisms in the promoter region rs572296424, rs55920607, rs113150889, of a gene can influence gene expression rs60249401, and a novel SNP were identified and may result in the altered uptake and within the SLC22A2 promoter region. clearance of drugs. Furthermore, five SNPs, i.e. rs59939658, rs60994312, rs115376067, rs11656096, OBJECTIVES and rs7213388 were identified within the To determine the haplotype structures SLC47A2 promoter region. The TF binding of SLC22A2 and SLC47A2 in the Xhosa site predictor PROMO (ALGGEN) was used population of South Africa and to determine for in-silico confirmation of cis-binding the functional significance these promoter elements to predict potential TF binding haplotypes may have on transcription sites within the promoter regions. factor (TF) binding and how it affects promoter activity. Also, to demonstrate CONCLUSIONS that haplotypes rather than individual We determined the haplotype structures SNPs regulate transcription and so doing of SLC22A2 and SLC47A2 for the Xhosa play a significant role in the response of population. We will further investigate individuals to drug treatment. the effects that the identified promoter haplotypes may have on promoter activity.

63 MOLECULAR CHARACTERISATION OF PROTEINS INVOLVED IN IRON- SULPHUR CLUSTER ASSEMBLY IN MYCOBACTERIA 1J. Arries, 2S. Adinolfi,1 M. Williams 1 Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University; 2 Department of Clinical Neuroscience, King’s College London, United Kingdom

BACKGROUND METHODS Mycobacterium tuberculosis (M.tb) remains We will use immunoprecipitation followed one of the world’s deadliest pathogens. by mass spectrometry to identify potential The ability of M.tb to survive within the interacting partners for the main FLAG- host is poorly understood, and efforts to tagged Fe-S cluster machinery. Potential elucidate these mechanisms of survival interactions will then be confirmed by mass are paramount in the fight against this spectrometry. Molecular techniques such disease. Iron-sulphur (Fe-S) clusters are as co-purification, cysteine desulphurase ubiquitous cofactors that are required for activity assay and Fe-S cluster reconstitution the maturation of various proteins, many will be used to characterise the relationship of which are involved in essential biological between proteins encoded by the SUF processes. Multiprotein complexes are operon. required for the in vivo assembly of Fe-S clusters, and the SUF system, encoded by RESULTS the Rv1460-Rv1461-Rv1462-Rv1463-csd- Until now, all constructs have been Rv1465-Rv1466 operon in M.tb, is thought successfully cloned and protein expression to be the major Fe-S cluster assembly performed. Optimisation of affinity machinery in this organism. This process purification and protein purification is near is poorly understood in mycobacteria, and completion, and final sample preparation it is currently unclear if proteins outside is underway for mass spectrometry analysis of this operon are involved in Fe-S cluster and subsequent validation by bimolecular assembly. fluorescence complementation. CONCLUSION OBJECTIVES With this work, we will establish the To identify novel proteins involved in Fe-S methodology for identifying novel protein- cluster assembly and characterise the protein interactions in mycobacteria and lay molecular relationship between proteins of the foundation for elucidating the process the SUF system. of Fe-S cluster assembly in mycobacteria.

64 PLASMA CYTOKINE BIOMARKERS TO PREDICT TUBERCULOSIS TREATMENT RESPONSE 1I. Boshielo, 1J. Peters, 1B. Kana 1 DST/NRF Centre of Excellence for Biomedical TB Research, University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa

BACKGROUND OBJECTIVES Tuberculosis (TB) is an infectious disease To determine the, 1) in vitro cytokine caused primarily by infection with response to DCTB created from different Mycobacterium tuberculosis (Mtb). clinical strains used to infect mouse TB has existed for millennia, killing macrophages; 2) cytokine response during approximately ten million people each early treatment of TB patients and identify a year. Even though most people who have biomarker signature to discriminate between active TB can be cured provided that slow and fast responders to treatment; 3) treatment is administered adequately, establish whether RIF/INH plasma levels the disease remains the leading cause of at different treatment time points can be death ranking above HIV-AIDS over the related to fast and slow response. past five years. The protracted treatment required to cure drug-susceptible TB is METHODS hypothesised to be attributable to the DCTB generation using two-sequential presence of non-replicating, drug-tolerant stress model. In vitro infection of mouse bacteria, termed differentially culturable macrophages with DCTB. Cytokine tubercle bacteria (DCTB). Consequently, biomarkers will be measured using a bead measuring the rate of DCTB clearance is array, while we will use high-performance central to understanding how TB treatment liquid chromatography to measure RIF and regimens can be shortened and to assess INH plasma levels. risk for recurrent disease. We identified RESULTS individuals from a longitudinal cohort of We anticipate that DCTB will induce a TB patients on standard chemotherapy, different cytokine response in fast and slow who were either able to clear DCTB within responders of TB treatment. the first two weeks of treatment and those wherein DCTB numbers persisted during CONCLUSION this period. These findings could potentially be used to identify individuals who would benefit from shorter treatment periods.

65 ADIPOSE TISSUE ANTIOXIDANT EXPRESSION IN VISCERAL AND SUBCUTANEOUS ABDOMINAL DEPOTS AND THE ASSOCIATION WITH CARDIOMETABOLIC RISK FACTORS IN AN OBESE POPULATION 1N. Ellman, 2J. Goedecke, 1A. Mendham, 3I. Marr, 3G. Stapleton, 1D. Keswell 1 Division of Exercise Science and Sports Medicine, University of Cape Town, South Africa; 2 Non- Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg; 3Chrysalis Clinic, Life Kingsbury Hospital, Cape Town

BACKGROUND dismutase (SOD) and catalase (CAT) using Abdominal fat, including visceral and Western blot. subcutaneous adipose tissue (VAT and SAT), is associated with insulin resistance RESULTS (IR), with VAT being more strongly Although SOD and CAT expression associated with IR than SAT. Few studies did not differ between VAT and SAT have investigated human adipose tissue (P=0.356 and 0.569, respectively), the (AT) antioxidant levels, and only one has associations between CMRF and SOD compared antioxidant expression between and CAT differed. SOD expression in SAT VAT and SAT. We hypothesize that adipose was positively associated with fat mass antioxidant levels are associated with index (FMI) (r=0.65, P=0.031), whereas cardiometabolic risk factors (CMRF) and expression of CAT in VAT was negatively that these associations differ by depot. associated with FMI and whole-body fat percentage (r=-0.69, P=0.039 and r=-0.73, OBJECTIVES p=0.01). Expression of SOD in SAT was To investigate depot-specific differences in positively associated with hs-CRP (r=0.65, AT antioxidant expression and its association P=0.019), and expression in VAT correlated with CMRF in an obese population. with glucose (r=0.63, P=0.037). In contrast, SAT expression of CAT was negatively METHODS associated with fructosamine (r=-0.77, We measured body composition (dual X-ray P=0.005). absorptiometry, basic anthropometry), measures of glycaemia including fasting CONCLUSIONS glucose, insulin, insulin resistance (HOMA- There were no depot differences in SOD IR), glycated haemoglobin (HbA1c %), and CAT expression. However, preliminary fructosamine along with lipid profiles, results suggest that SOD and CAT may be high-sensitivity C- reactive protein (hs- associated with systemic inflammation and CRP) and leptin in obese South African glucose metabolism. We propose that SOD participants (n=14; 71% female, mean age may be upregulated in response to obesity 41±10.0). Total protein lysates isolated and systemic inflammation and CAT may from abdominal SAT and VAT samples were be reduced with obesity and increased analysed for key antioxidants superoxide glycaemia.

66 EFFECT OF ROUX-EN-Y GASTRIC BYPASS SURGERY VERSUS A CONVENTIONAL WEIGHT-LOSS PROGRAMME ON CARDIOMETABOLIC RISK FACTORS AT ONE AND SIX MONTHS POST-INTERVENTION 1N. Ellman, 2J. Goedecke, 1A. Mendham, 3K. Adams, 4I. Marr, 4G. Stapleton, 1D. Keswell 1 Division of Exercise Science and Sports Medicine, University of Cape Town, South Africa; 2 Non- Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg; 3 Department of Plastic Surgery, University of Cape Town, 4 Chrysalis Clinic, Life Kingsbury Hospital, Cape Town

BACKGROUND (VAT) decreased similarly between groups Few studies have compared the effects at 1-month post-intervention (P<0.05), of Roux-en-Y gastric bypass surgery but a greater percentage decrease was (RYGBS) versus conventional weight-loss observed in RYGBS vs. CWLP participants programmes (CWLP) on cardiometabolic at six months post-intervention (40.9±8.8% risk factors (CMRF). vs. 17.3±28.6%, P=0.025). In RYGBS participants only, LDL-cholesterol and OBJECTIVE total cholesterol decreased at both time We aimed to test the hypothesis that points relative to baseline (23.9±12.4% RYGBS improves CMRF to a greater extent and 27.2±21.2%; 19.0±10.7% and than CWLP. 20.2±18.5%, P<0.01), whereas HOMA-IR (49.4±31.3%, P= 0.044) and leptin levels METHODS (62.35±22.8%, P<0.01) only decreased at Body composition (dual X-ray six months relative to baseline. Changes absorptiometry), insulin resistance (HOMA- in cholesterol, HOMA-IR and leptin levels IR), glycated haemoglobin (HbA1c %), were dependent on changes in BMI high-sensitivity C-reactive protein (hs-CRP), (P>0.05). Although RGYBS, and not CWLP, leptin and lipid profiles were measured reduced HbA1c percentage at one month in South African participants undergoing (5.7±4.4, P=0.017), and hs-CRP (64.0±19.8, RYGBS (n=12) and a CWLP (n=12) at P<0.001) and triglycerides (20.7±26.2, baseline and at one and six months post- P=0.047) at six months, the percentage intervention. change was not different between groups RESULTS (P>0.05). Although RYGBS participants had a higher body mass index (BMI) (46.2±7.0 CONCLUSION RYGBS results in greater reductions in vs. 36.6±8.3 kg/m2, P=0.005) than those CMRF, specifically VAT, insulin resistance following CWLP at baseline, CMRF did and lipid profile, compared to CWLP. Our not differ. RYGBS resulted in a greater further analysis will focus on the molecular percentage decrease in participants’ mechanisms involved in the improvement BMI compared to CWLP at one and six of insulin sensitivity, with emphasis on months post-intervention (9.9±2.3% vs. oxidative stress. 4.1±3.0% and 23.0±3.3% vs. 9.5±8.3%, P<0.001 for both). Visceral adipose tissue

67 INFLUENCE OF LESSERTIA FRUTESCENS AND ECHINACEA PURPUREA ON THE BIOAVAILABILITY AND METABOLISM OF ETHINYLESTRADIOL BASED CONTRACEPTIVES 1,2N. Hlengwa, 2A. Basson, 1C. Awortwe, 1S. Bowles, 1C. Muller 1 Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa; 2 Department of Biochemistry and Microbiology, University of Zululand, Kwa- Dlangezwa, South Africa

BACKGROUND METHODS Lessertia frutescens and Echinacea Transport experiments across Caco-2 purpurea extracts are commonly used monolayers, using EE, EES and EEG were herbal immune boosters by immune- conducted in the presence and absence compromised individuals, including HIV of the herbal extracts. We assessed the patients. Previous findings suggested that effect of herbal extracts on the clearance these extracts interact with cytochrome P450 and metabolism of EE in human liver enzymes and drug transporters. Therefore, microsomes, S9 fractions and C3A cells. the aim is to investigate whether the co- use of Lessertia frutescens or Echinacea RESULTS purpurea influences the rate of metabolism The rate of transport of EES and EEG and efficacy of α 17 -ethinylestradiol (EE)- were increased by the addition of herbal 7 2 6 based oral contraceptives. extracts (4.78 x 10 cm/s , 1.23 x 10 cm/ s2), respectively in Caco-2 cells. Human OBJECTIVES liver microsomes and S9 fractions To assess the effect of herbal extracts on revealed an increase in the clearance the intestinal uptake and efflux of EE, and (0.42 ± 0.033, 0.06 ± 0.02) of EE in the its pharmacologically active metabolites presence of both extracts, respectively. (17α-ethinylestradiol-3-O-sulfate (EES) and These results were further confirmed by 17α-ethinylestradiol-3-O-glucuronide (EEG)) induction experiments, which validated using Caco-2 cell model. To evaluate the the effect of the herbal extracts increasing effect of herbal extracts on EE metabolism gene expression of a major efflux protein using human liver microsomes and human (ABCB1 (2.86±0.95, 2.38±1.49)) and a S9 liver fractions. To determine the effect drug transporter (SLCO1B39 (1.81±1.80, of herbal extracts on mRNA expression of 0.454±0.19)) in C3A cells. the relevant major CYP enzymes and drug transporters using C3A liver-cell model. CONCLUSION Co-administration of the herbal extracts may lead to herb-drug interactions, reducing the efficacy of EE-based oral contraceptives eventually leading to contraceptive failure.

68 THE EFFECTS HERBAL TEAS (ROOIBOS AND HONEYBUSH) IN THE REGULATION OF INFLAMMATORY RESPONSES DURING SKIN CARCINOGENESIS 1L. Keet, 2S. Abel, 2M. Lilly, 1A. Louw 1 Department of Biochemistry, University of Stellenbosch; 2 Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology

BACKGROUND that were seeded previously for 6 hours in Keratinocyte UV exposure may be associated Dulbecco’s modified Eagle’s medium. After with multiple physiological response events irradiation, the cells were incubated for in the human skin demonstrating a complex an additional 24 hours and inflammatory and multifaceted biological process. The markers monitored utilising the Bio-plex resultant inflammatory responses involve Pro assay. Non-irradiated cells were also the production of various inflammatory monitored after 18 hours of treatment and cytokines, chemokines and the induction 48 hours after seeding. of cell death. Several studies have shown the anti-inflammatory and subsequent anti- RESULTS tumour activities of rooibos and honeybush Before UVB exposure, cell viability markers by the topical application to mouse skin. were not detrimentally affected. The herbal The mixture of polyphenolic compounds extracts stabilised the keratinocytes by is known to act as antioxidants and likely reducing the production of the different to prevent oxidant-induced cell damage, cytokine biomarkers following the 18 hours’ playing a chemo-preventive role. pre-exposure. The reduction of several of these biomarkers is retained after 24 hours OBJECTIVE in the absence of UVB exposure. Following Multiple inflammatory markers in UVB irradiation, a memory effect seems keratinocytes will be monitored before and to exist with the reduction of cytokine after exposure to UVB light. biomarkers associated with the subsequent inflammatory response. This suggests a METHODS direct anti-inflammatory potential. A keratinocyte/UVB exposure model was utilised to investigate these effects CONCLUSIONS with herbal extracts of rooibos and three The rooibos and C. subternata extracts were honeybush subspecies as inflammatory the most effective in protecting against agents. Freeze-dried aqueous herbal tea UVB-induced effects. Understanding the extracts prepared to the desired dilutions molecular mechanisms that underlie these were added 18 hours before UVB exposure processes is of importance in devising (80 mJ/cm2) to HaCaT keratinocyte cells chemo-preventive interventions.

69 AN ANTI-STEATOTIC EFFECT OF ASPALATHIN-RICH GREEN ROOIBOS EXTRACT ON OLEIC ACID INDUCED STEATOSIS IN C3AS 1,2N. Khuboni, 1C. Muller, 2R. Mosa, 2A. Kappo, 1K. Gabuza 1 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa; 2 Department of Biochemistry and Microbiology, University of Zululand, Kwadlangezwa, South Africa

BACKGROUND In vivo C57BL6/J (db/db) or (db/+) diabetic/ Non-alcoholic fatty liver disease (NAFLD) is NAFLD mice were treated with GRT over a major cause of liver disease worldwide. a 10- or 16-week period. Food and water The incidence of NAFLD is expected to intake, body and liver weight, and fasting escalate dramatically with the upsurge in glucose were monitored. A week before the metabolic diseases, including obesity and end of the treatment period, oral glucose type 2 diabetes. Rooibos helps to improve tolerance tests were performed. After metabolism and has demonstrated each treatment period, the animals were hepatoprotective effects against carbon terminated, and liver samples collected for tetrachloride (CCl4) and tert-butyl histological, gene and protein analysis. hydroperoxide induced hepatotoxicity in rodents. RESULTS Microscopic images showed decreased OBJECTIVE lipid content by <80% in steatotic C3A cells To assess the modulatory or (indicated by low intensity of ORO staining) hepatoprotective effect of an aspalathin- following treatment with 10 and 100 µg/ rich Rooibos (Afriplex-GRT) extract in in- ml GRT. The reduction was comparable to vitro and in-vivo models of NAFLD. pioglitazone (control drug). Furthermore, in db/db mice, GRT improved glucose METHODS tolerance and reduced the liver weight to Oleic acid was used to induce steatosis body weight ratio. C3A liver cells. C3A cells were treated with pioglitazone or GRT for 24 hours, CONCLUSION either during or after (post-treatment) the GRT-modulated lipid accumulation induced induction of steatosis by 1 mM oleic acid by oleic acid in C3A cells and the reduction for 24 hours. Oil red O staining and MTT of relative liver weights in diabetic NAFLD assay were performed to determine lipid db/db mice suggest that GRT could help accumulation and cell viability, respectively. ameliorate NAFLD.

70 UNDERSTANDING THE ROLE INTER-INDIVIDUAL GENETIC VARIATION PLAYS IN THE DEVELOPMENT OF UNCONTROLLED HYPERTENSION IN PATIENTS WITH CONCOMITANT TYPE 2 DIABETES MELLITUS AT TYGERBERG ACADEMIC HOSPITAL, WESTERN CAPE SOUTH AFRICA 1,2S. Mabhida, 3M. Conradie, 2L. Mabasa, 1,2M. Benjeddou, 2S. Bowles, 2,4R. Johnson 1 Department of Biotechnology, University of the Western Cape, Bellville, South Africa; 2 Biomedical Research, Innovation Platform, South African Medical Research Council, Tygerberg; 3 Division of Endocrinology, Stellenbosch University, Tygerberg; 4 Division of Medical Physiology, Stellenbosch University, Tygerberg, South Africa

BACKGROUND determine the effect of genetic variants Hypertension (HTZ) affects 1 billion on the pharmacokinetic profile of specific individuals globally of which 50% have hypertensive drugs for each haplotype. controlled blood pressure. HTZ is a major and modifiable risk factor for cardiovascular METHODS disease that frequently coexists with type Buccal swabs will be collected from 2 diabetes mellitus (T2DM). In recent uncontrolled hypertensive patients living years, the mechanism that underpins with and without T2DM, who are on a uncontrolled hypertension and its effect on multidrug combination therapy. DNA treatment outcome has been the subject from patients, with and without controlled of intensive investigation. A growing body hypertension, will be isolated and genotypic of evidence suggests that inter-individual analysis of SNP variants from several genes variability to a drug’s response affects will be determined using the TaqMan efficacy and toxicity that result in HTZ allelic discrimination assay. Genetic variants remaining uncontrolled. This variability and will then be evaluated and grouped to associated clinical problems complicate the establish a common haplotype associated standard treatment protocols. Therefore, with uncontrolled HTZ. Thereafter, in this study, we aim to identify inter- serum will be collected to determine individual variation in DNA sequence and the pharmacokinetic profile of specific relate it to a drug’s pharmacokinetics and hypertensive drugs for each haplotype pharmacodynamics for tailoring treatment using tandem liquid chromatography- to a patient’s specific genotype. mass spectrometry. This profile will then be compared to haplotypes of selected genes OBJECTIVES to establish a genetic profile that could To assess genotypic analysis of single possibly be used by clinicians to predict to nucleotide polymorphism (SNP) variants in which antihypertensive drug the individual several genes associated with uncontrolled is most likely to respond. HTZ; evaluate and group genetic variants to establish a common haplotype; and RESULTS & CONCLUSION: Not applicable.

71 BACKGROUND QUALIFICATIONS, SELF-PERCEIVED COMPETENCIES AND LEADERSHIP DEVELOPMENT PRACTICES AMONG PUBLIC-SECTOR HOSPITAL MANAGERS IN KWAZULU-NATAL 1N. Mabuza 1 Department of Public Health and Nursing, School of Health Sciences, University of KwaZulu-Natal

BACKGROUND we will employ a total population sampling Leadership development, a concept technique among senior hospital managers rooted in different theoretical frameworks, at public hospitals in KwaZulu-Natal. A self- ranges from behavioural science to administered questionnaire comprising business and other disciplines. The closed and open-ended questions will extensively researched concept has been be used for descriptive statistics and practised in the international business correlation analysis with a significance level sector gaining research interest within the of p=0.05. Because of the poor response global healthcare industry around 2003. rate, a scoping review developed by the Currently, it is poorly explored within the Joanna Briggs Institute will be conducted South African healthcare sector. Leadership parallel to the main study. A scoping review development practices are tools used to entails an exploratory literature search develop the required interpersonal skills, providing evidence on a topic irrespective which can be developed in conjunction with of study quality, which is useful to examine academic qualifications. In South Africa, emerging areas, clarify key concepts and these practices have not been explored identify gaps. in public hospitals. The Department of Health is attending to the management RESULTS needs through implementing changes and Data collection in progress. introducing the National Health Insurance. CONCLUSIONS OBJECTIVES Current methods applied to develop To describe, 1) Professional profiles of leadership and managerial competencies senior hospital managers in the public among hospital managers working within sector; 2) Their preparedness for the job the public healthcare sector will be role; and 3) The leadership development reported. Current leadership development and succession planning practices of public practices applied within the African sector healthcare managers. continent including the processes followed to apply the practices will be discussed. METHODS The goal of this paper is to add knowledge Using a sequential explanatory mixed- by publishing research findings obtained methods cross-sectional research design, from the study.

72 THE ASSOCIATION BETWEEN POLYMORPHISMS IN THE VITAMIN D RECEPTOR AND METABOLIZING ENZYME GENES AND TYPE 1 DIABETES MELLITUS IN THE SOUTH AFRICAN INDIAN POPULATION 1N. Malaza, 1E. Cave, 1,2C. Padoa 1 Chemical Pathology, University of Witwatersrand, Johannesburg; 2 National Health Laboratory Service, Johannesburg

BACKGROUND participants (n=64) were recruited from Vitamin D plays an immunoregulatory SANBS blood drives. All participants were role in type 1 diabetes (T1D) through the genotyped by PCR-RFLP for three VDR vitamin D receptor (VDR) present in the polymorphisms (rs1544410, rs7975232 and pancreatic and immune cells. Increased rs713236) and rs10741657 in the CYP2R1 levels of vitamin D mediate the shift from gene. the Th1 pathway, which is responsible for the destruction of pancreatic β cells to the RESULTS Th2 pathway. Polymorphisms in the VDR There was a significant difference in and CYP2R1 genes have been shown to the allele frequency for VDR rs7975232 be associated with T1D. Little is known between patients and controls (A allele: 0.74 about the effect of these polymorphisms vs. 0.48, respectively; p=0.000). Similarly, on the development of T1D in the South the A allele of CYP2R1 rs10741657 was African Indian population. Thus, we aimed significantly higher in patients compared to determine the frequency of these to controls ((0.44 vs. 0.27, respectively; polymorphisms and their association with p=0.007). No differences in allelic the development of T1D in the South frequencies between patients and controls African Indian population. were seen for rs1544410 and rs731236 (p=0.054 and 0.28, respectively). OBJECTIVES To determine the frequency of the CONCLUSIONS polymorphisms in the South African Indian The rs7975232 and rs10741657 population and to determine if they are polymorphisms are associated with the associated with the development of T1D. development of T1D in the South African Indian population. The belief is that these METHODS polymorphisms result in defective vitamin T1D patients (n=52) were recruited from D production and signalling leading to a Charlotte Maxeke Johannesburg Academic shift from the Th2 (anti-inflammatory) to the and Inkosi Albert Luthuli Central Hospitals. Th1 (pro-inflammatory) pathway resulting in Healthy non-diabetic South African Indian β-cell death.

73 INVESTIGATION OF THE INFLUENCE OF GENETIC VARIATION ON THE EXPRESSION EFFICIENCY OF THE PROMOTER REGION OF SLC47A2/ MATE-2K GENE 1C. Masilela, 2R. Johnson, 1M. Benjeddou 1 Precision Medicine Unit, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape; 2 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg

BACKGROUND using a salt lysis method and quantified Solute carrier family 47, member 2 using a Nanodrop Spectrophotometer. (SLC47A2) also known as multidrug and The promoter region was sequenced to toxin extrusion 2 (MATE2-K), plays an identify the different single nucleotide important role in the excretion of the polymorphisms (SNPs) and haplotypes anti-diabetic drug metformin. Previous present in the Zulu population. DNA studies have established that genetic fragments representative of the haplotypes polymorphisms in the promoter region of identified were cloned into a promoter- the MATE-2K gene are likely to directly less vector (pGluc basic 2 vector) and influence the pharmacokinetics and inter- expressed in immortalised human kidney individual variability in metformin response. cells (HEK293). The expression efficiency Therefore, accounting for the variability in was monitored by measuring fluorescence this gene is important in understanding using flow cytometry. the impact of genetic variation in drug transport as well as response. RESULTS The promoter region of MATE-2K was OBJECTIVE sequenced in 96 samples. Six SNPs and 15 To evaluate the expression efficiency of the promoter haplotypes were identified. The promoter region of the MATE-2K gene in level of expression and relative expression haplotypes associated with the promoter efficiency was determined by flow within the indigenous Zulu population of cytometry and statistical analyses. South Africa. CONCLUSION METHODS This project will generate novel Buccal swab samples were collected from pharmacogenomics data that are relevant a Zulu population. DNA was extracted in the context of precision medicine.

74 WHOLE-GENOME TRANSPOSON MUTAGENESIS TO ELUCIDATE THE

GENETIC REQUIREMENTS FOR VITAMIN B12 BIOSYNTHESIS AND ASSIMILATION IN MYCOBACTERIA 1,2R.D. Mbau, 1,2G.T. Mashabela, 1,2V. Mizrahi, 1-3R. Mukherjee, 1,2D.F. Warner 1 SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa; 2 Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; 3 Division of Biology, Indian Institute of Science Education and Research, Tirupati, India

BACKGROUND dependent methionine synthase, MetH, Recent comparative genomics analyses is essential for viability. Following growth have suggested that an altered capacity for of the metE mutant in rich laboratory vitamin B12 biosynthesis might represent medium, genomic DNA was extracted, a critical step in the evolution of the amplified by PCR, and subjected to high- pathogenic Mycobacterium tuberculosis throughput sequencing to quantify all complex strains from a non-pathogenic Tn junctions. Thereafter, the library was ancestor. However, resolving the full gene cultivated in defined minimal medium complement involved in the complex, multi- to enable identification of conditionally step pathways for vitamin B12 biosynthesis, essential genes. assimilation, and salvage in different mycobacterial species is enormously RESULTS challenging. To address this problem, we A ∆metE library of 400,000 Tn insertion have adopted a genome-scale approach mutants (cfu/ml) was generated. Analysis to yield a detailed genetic map of de of the resulting sequencing data revealed that, Of the 6,716 genes in the M. novo vitamin B12 biosynthesis and salvage in mycobacteria, as well as to elucidate smegmatis genome, 213 genes were previously unknown genes or regulatory identified as essential for growth on LB agar while 312, 314, and 309 genes were elements involved in mycobacterial B12 identified as essential in unsupplemented, metabolism. B12-supplemented or cobalt-supplemented OBJECTIVE Sauton’s minimal medium, respectively. To elucidate the genetic requirements for CONCLUSIONS vitamin B12 biosynthesis and assimilation in the non-pathogenic mycobacterial model The metE library represents a valuable organism, M. smegmatis. repository of Tn insertion mutants for genome-wide conditional essentiality METHODS analyses in defined minimal media. These We applied a combination of whole- studies are underway and will enable the genome Tn mutagenesis and next first validated elucidation of the full vitamin generation sequencing (Tn-seq) in M. B12 gene repertoire in mycobacteria. smegmatis ΔmetE, a gene-deletion mutant in which the function of the alternative, B12-

75 DEVELOPMENT AND VALIDATION OF ANTIRETROVIRAL DRUG LEVELS FOR THERAPEUTIC DRUG MONITORING USING DRIED BLOOD SPOTS 1S. Modiba, 1,2T. Snyman 1 Chemical Pathology, University of the Witwatersrand; 2 National Health Laboratory Service, Johannesburg

BACKGROUND limit of quantification, specificity, sensitivity, Despite global efforts to halt the human recovery and stability for each of the drugs immunodeficiency virus (HIV) epidemic, used. the number of individuals living with HIV continues to rise. Plasma concentrations RESULTS of antiretroviral (ARV) drugs are frequently The following transitions were used for used for therapeutic drug monitoring. analysis. The parent drug: with its multiple- Dried blood spot (DBS) sampling offers reaction monitoring transitions: Efavirenz a patient-friendly and easy alternative to (EFV): 315.99 > 243.94; lamivudine (3TC): plasma sampling. 230.03 > 112.00; lopinavir (LPV): 629.50 > 447.10; and ritonavir (RTV): 721.20 > 170.91. OBJECTIVES The assay was linear over the concentration To develop and validate a method for the ranges tested 119-833, 323-2360, 104- measurement of ARVs in DBS using ultra- 6640 and 370-5685 ng/ml for 3TC, EFV, pressure liquid chromatography in tandem RTV and LPV, respectively. Accuracy, inter- with mass spectrometry (UPLC-MS/MS). and intra-day precision gave a coefficient of variation of 20%, 7%, 6% and 6% for METHODS 3TC, EFV, RTV and LPV, respectively. The Samples were spotted onto the collection limit of detection and limit of quantification cards and left to dry overnight. Each for each of the compounds were 10, 86 and DBS was punched out and treated with a 36.2 ng/ml for 3TC; 17.58 and 58.6 ng/ml mixture of 0.1% formic acid in methanol for EFV; 54.51 and 181.7 ng/ml for LPV; and and 0.2 M zinc sulphate heptahydrate in 4.62 and 15.4 ng/ml for RTV. water (50:50 v/v) containing the deuterated internal standards. Ten microliters of the CONCLUSION extract were injected onto Shimadzu Method validation is near completion and 8060 UPLC-MS/MS for analysis. Linearity, patient recruitment has commenced. accuracy, precision, limit of detection and

76 DEVELOPMENT AND VALIDATION OF ANTIRETROVIRAL DRUG LEVELS FOR THERAPEUTIC DRUG MONITORING USING DRIED BLOOD SPOTS 1S. Modiba, 1,2T. Snyman 1 Chemical Pathology, University of the Witwatersrand; 2 National Health Laboratory Service, Johannesburg

BACKGROUND limit of quantification, specificity, sensitivity, Despite global efforts to halt the human recovery and stability for each of the drugs immunodeficiency virus (HIV) epidemic, used. the number of individuals living with HIV continues to rise. Plasma concentrations RESULTS of antiretroviral (ARV) drugs are frequently The following transitions were used for used for therapeutic drug monitoring. analysis. The parent drug: with its multiple- Dried blood spot (DBS) sampling offers reaction monitoring transitions: Efavirenz a patient-friendly and easy alternative to (EFV): 315.99 > 243.94; lamivudine (3TC): plasma sampling. 230.03 > 112.00; lopinavir (LPV): 629.50 > 447.10; and ritonavir (RTV): 721.20 > 170.91. OBJECTIVES The assay was linear over the concentration To develop and validate a method for the ranges tested 119-833, 323-2360, 104- measurement of ARVs in DBS using ultra- 6640 and 370-5685 ng/ml for 3TC, EFV, pressure liquid chromatography in tandem RTV and LPV, respectively. Accuracy, inter- with mass spectrometry (UPLC-MS/MS). and intra-day precision gave a coefficient of variation of 20%, 7%, 6% and 6% for METHODS 3TC, EFV, RTV and LPV, respectively. The Samples were spotted onto the collection limit of detection and limit of quantification cards and left to dry overnight. Each for each of the compounds were 10, 86 and DBS was punched out and treated with a 36.2 ng/ml for 3TC; 17.58 and 58.6 ng/ml mixture of 0.1% formic acid in methanol for EFV; 54.51 and 181.7 ng/ml for LPV; and and 0.2 M zinc sulphate heptahydrate in 4.62 and 15.4 ng/ml for RTV. water (50:50 v/v) containing the deuterated internal standards. Ten microliters of the CONCLUSION extract were injected onto Shimadzu Method validation is near completion and 8060 UPLC-MS/MS for analysis. Linearity, patient recruitment has commenced. accuracy, precision, limit of detection and

77 METABOLIC PROFILE OF RAT INSULINOMA BETA-CELL SPHEROIDS (INS-1) 1,2Y. Ntamo, 1-3C.J.F. Muller, 2A.M.P. Kappo, 1,2J. Louw, 1,3N. Chellan 1 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa; 2 Department of Biochemistry and Microbiology, University of Zululand, Kwa-Dlangezwa, South Africa; 3 Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa

BACKGROUND medium, supplemented with low (11 mM) Cell culture is commonly used to study and high glucose (16.7 mM). Additionally, cellular pathophysiology of conditions such relevant survival and functional parameters as type 2 diabetes (T2D). However, standard such as viability and insulin secretion were cell culture is grown on flat, polystyrene investigated. plastic surfaces that do not represent the three-dimensional architecture of tissue in RESULTS vivo. These cultures lack some important Culture conditions were optimised for environmental cues from the cellular INS-1 beta-cell spheroids growth up microenvironment, such as cell-to-cell to ± 2 months. Their viability increased interaction and long-term, uninterrupted proportionally with time in culture from growth. To increase the physiological day one to 44 (5852 ± 137.6 RLU to 53568 relevance of cell culture, microgravitational ± 937.9 RLU, p<0.0001), respectively. three-dimensional culture systems have Additionally, at a functional level, spheroids been developed that produce tissue-like were responsive to glucose-stimulated spheroids. insulin secretion assays with 16.7 mM glucose (week 4 (15.11±1.55 vs 2.65±0.15 OBJECTIVE ng/mL, p<0.001), week 5 (14.15±1.05 To develop a method to produce pancreatic vs 1.95±1.05 ng/mL p<0.001), week 6 (INS-1) beta-cell spheroids. (17.95±2.25 vs 2.85±0.05 ng/mL, p<0.001), week 7 (12.70±1.00 vs 2.15±1.05 ng/ METHODS mL, p<0.001) and week 8 (11.35±1.35 vs The CelVivo BAM, microgravitational culture 2.65±1.05 ng/mL, p<0.001), respectively. system was used to culture INS-1 cells into beta-cell spheroids. Briefly, INS-1 cell CONCLUSION clusters were produced in AggreWell plated We have successfully established an in vitro, (STEMCELL technologies), transferred 3D-culture model of beta-cell spheroids into a rotating bioreactor of the CelVivo which promises to be more physiologically BAM system and then grown for extended relevant and could be very useful in periods for further experimentation. These understanding the pathophysiology of spheroids were cultured in normal RPMI beta-cell metabolic conditions such as T2D.

78 SUSTAINED AUTOPHAGIC FLUX WITH CELL DEATH ONSET IN AN IN VITRO MODEL OF ALZHEIMER’S DISEASE 1C. Ntsapi, 1B. Loos 1 Non-Communicable Diseases Unit, SAMRC/Division of Medical Physiology, Department of Physiological Sciences, Faculty of Science, University of Stellenbosch, Stellenbosch

BACKGROUND control and regulation of the autophagic Alzheimer’s disease (AD) is the most machinery in AD. common, incurable form of dementia, affecting more than 35 million people OBJECTIVES worldwide. The amyloid cascade To determine the effects of APP hypothesis suggests that the widespread overexpression on (i) autophagic flux, (ii) neurodegeneration found in AD patients APP and Aβ protein clearance, and (iii) cell is caused by the accumulation of amyloid- death onset. beta peptide (Aβ), which is derived from the METHODS amyloid precursor protein (APP). Although Using N2aSwe cells stably overexpressing extracellular aggregates of Aβ serve as APP as our in vitro model of AD, we one of the primary hallmark pathologies (i) quantified protein expression in the required for a diagnosis of AD, deficits absence and presence of Bafilomycin in the autophagy-lysosomal pathway are A1 (BafA1) treatment using western blot thought to precede the accumulation of analysis, and (ii) characterised the cellular Aβ. Deficits in this pathway manifest as ultrastructure in the absence and presence defective autophagy, the major cellular of BafA1 using transmission electron quality control system that degrades microscopy analysis. damaged organelles and potentially toxic protein aggregates by delivering them to RESULTS the lysosomes for degradation. In the AD Autophagic flux is increased with APP brain, Aβ-laden autophagic vesicles (AVs) overexpression and remains enhanced accumulate in the dystrophic neurites, even with cell death onset. thus linking impaired autophagy to Aβ metabolism. However, it is unclear whether CONCLUSION accumulated AVs reflect an increase in Autophagic flux remains functional autophagic flux, or that the end stage of even with late APP overexpression and AVs clearance is impaired. Autophagic flux increased Aβ neurotoxicity suggesting is a measure of autophagic degradation that autophagy activity can be modulated activity, and the precise measurement of throughout the duration of AD progression this process is crucial to understanding the for the first time.

79 INVESTIGATING VACCINE HESITANCY AND VALIDATING A MEASURING TOOL IN THE WESTERN CAPE PROVINCE 1E.O. Oduwole, 1,2H. Mahomed, 3,4C.S. Wiysonge 1 Division of Health Systems and Public Health, Department of Global Health, Stellenbosch University; 2 Cape Metro Health Services, Western Cape Government; 3 Division of Epidemiology and Biostatistics, Department of Global Health, Stellenbosch University; 4 Cochrane South Africa, South African Medical Research Council, Tygerberg

BACKGROUND existing vaccine hesitancy measurement Vaccine hesitancy, defined as the delay in tools, irrespective of where they have been acceptance or refusal of vaccination despite developed or validated. In the second the availability of vaccination services, is an phase, we will utilise iterative testing emerging global problem. Contributing methodology to adapt and validate the to low and sub-optimal vaccine coverage, Vaccine Hesitancy Scale among parents it can lead to intermittent outbreaks of of children age one year and younger. vaccine-preventable diseases. The paucity They will be drawn from the three strata of of research and the lack of validated geographical dwelling areas in the Western measurement tools in South Africa is of Cape Province, South Africa as described concern. by Statistics South Africa. The estimated total sample size for the study will be OBJECTIVES greater than 500 participants. To adapt and validate a survey tool to investigate vaccine hesitancy, we will RESULTS conduct 1) an overview of reviews on The research is currently at the protocol vaccine hesitancy, and 2) a comprehensive approval stage, hence there are no data review of current tools to measure vaccine available. hesitancy. 3) We will modify and validate the Vaccine Hesitancy Scale in South Africa. CONCLUSIONS We anticipate that the two reviews and the METHODS validation study will contribute immensely This quantitative study will consist of two to the existing body of knowledge on phases, a synthesis of existing research vaccine hesitancy on the local and global and a primary study. Phase one (evidence scale. The validated tool will be valuable synthesis phase) will involve (a) an overview in reducing the knowledge deficit in of existing systematic reviews on vaccine addressing vaccine hesitancy in South hesitancy; and (b) a scoping review of Africa and similar settings.

80 GENOME-WIDE ASSOCIATIONS BETWEEN HOST GENOTYPES AND M. TUBERCULOSIS 1S. Pitts 1,2S. Pitts, 1M. Möller, 1H. Schurz,1E. Streicher, 1R. Warren, 3T. Thye, 4,5S. Niemann, 1E. Hoal, 1,2G. van der Spuy, 1,2G.C. Tromp, 1C. Kinnear 1 DST-NRF Centre of Excellence for Biomedical Tuberculosis Research; 2 South African Tuberculosis Bioinformatics Initiative; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa; 3 Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg Germany; 4 Molecular and Experimental Mycobacteriology, Forschungszentrum Borstel, 23845 Borstel, Germany; 5 German Center for Infection Research, Borstel Site, 23845 Borstel, Germany

BACKGROUND RESULTS Tuberculosis (TB) is a complex disease The cohort was dominated by LAM, caused by infection with Mycobacterium followed by the Haarlem/LCC, Beijing/ tuberculosis (M. tb). While most infected, CAS1, Other, and Quebec superclades. immune-competent individuals remain MLR was performed using ~7 million asymptomatic, approximately 10% SNPs for 445 samples, and the five M. tb will develop active disease. Numerous superclades. The strongest association was studies have investigated the association with SNP rs9389610 (g.139039029G>A) of candidate genes with TB, and with on chromosome 6, at a p-value of 1.6x10- different M. tb clades, with one recent 7. Individuals with the A allele of this SNP study investigating genome-wide were twice as likely to be infected with a associations in a Thai cohort. member of the Beijing/CAS1 superclade, as compared to the Haarlem/LCC (OR: OBJECTIVE 0.49) or LAM (OR: 0.46) superclades. In this study, the aim was to investigate genome-wide association(s) between the CONCLUSIONS host genotype and the genome of the Although the association did not reach infecting M.tb pathogen. genome-wide significance, the results suggest replication of this approach in METHODS a larger cohort of this population may Sputum and blood samples were provide significant associations with the collected from TB patients residing in a infecting M. tb clade, thereby improving suburb of Cape Town. Genotyping was our understanding of TB pathobiology. performed using the Affymetrix 500k SNP This is the first study to analyse associations array, and M. tb clades were identified between gene variants and M. tb using spoligotyping and IS6110 RFLP. superclades at a genome level, and this Genotypes passing strict quality control working method will now be used to filters were phased followed by imputation. investigate a Ghanaian cohort. Multinomial logistic regression (MLR) was performed using SNP test and the standard genome-wide significance cut-off of alpha = 5 x 10-8 was used.

81 PREVENTION OF DOXORUBICIN-INDUCED CARDIOTOXICITY: A MECHANISTIC STUDY 1,2N.F. Sangweni, 1L. Mabasa, 1,2B. Huisamen, 2D. van Vuuren, 1,2R. Johnson 1 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa; 2 Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa

BACKGROUND between G. africana and ATC (herb-drug Anthracyclines (ATCs) are a class of highly interaction). To determine the efficacy of potent chemotherapeutic agents used to compounds specific to G. africana in the treat various types of malignancies such prevention of aCMP in an in vivo neoplastic as breast cancer. Although effective, the or non-neoplastic Wistar rat model. therapeutic index of these drugs is drastically reduced because of their cardiotoxic side METHODS effects. Following ATC treatment, the Blood from breast cancer patients in myocardial insult resulting in months for remission will be collected at predetermined acute-toxicity or years for chronic-toxicity, time periods to test for known cardiac have been demonstrated in studies. biomarkers using the cardiac Troponins and Therefore, early preclinical detection of NT-proBNP serum ELISA kits. The inhibitory patients at risk of anthracycline-induced or inducing effect of compounds specific to cardiomyopathy (aCMP) and preventative G. africana will be measured using Vivid treatment strategies can be employed to recombinant cytochrome P450 enzymatic attenuate the resulting cardiotoxicity. To assays. Then, to investigate the efficacy this end, compounds from Galega africana, of these compounds in preventing aCMP, which possess cardioprotective and anti- 7-week-old female, neoplastic (chemically cancer properties, could aid in alleviating induced with MBA for two weeks) and non- aCMP. Therefore, in this study we will neoplastic, Wistar rats will be co-treated investigate the cardioprotective effect of with compounds specific toG. africana and these compounds and elaborate on the doxorubicin for six weeks. Three months proposed mechanism in preventing aCMP. after cessation of treatment, animals will be terminated, and blood and tissue collected OBJECTIVES for subsequent histological, biochemical To screen the serum of breast cancer and protein and gene expression analysis. patients for early predictive parameters related to aCMP. To understand the RESULTS & CONCLUSION underlying pharmacokinetic interactions Not applicable.

82 A PEPTIDOGLYCAN RECYCLING AND AMIDATION ENZYME IN MYCOBACTERIUM TUBERCULOSIS AS A NEW DRUG TARGET FOR TUBERCULOSIS 1M. Shaku, 1B. Kana 1 DST/NRF Centre of Excellence for Biomedical TB Research, Wits University, Johannesburg

BACKGROUND of MurT depleted cells and for cellular Mycobacterium tuberculosis (Mtb), localisation of MurT-GFP. The mycobacterial assembles a complex cell wall with cross- protein fragment complementation assay linked peptidoglycan (PG) being essential was used to determine MurT interacting for cellular integrity. PG is composed of partners. glycan and peptide components, the latter containing amidated D-glutamate, RESULTS which is essential for PG cross-linking. PG MurT is essential for mycobacterial growth. recycling and amidation in gram-positive MurT was found to be required for PG bacteria is facilitated by murein peptide amidation. Depletion of MurT causes cell ligase (MurT), and in this study, we focused death. Spatial localisation of MurT-GFP on characterisation of the mycobacterial reveals that MurT localises at the cell poles homologue for this enzyme. and cell division septum. Bioinformatic and biochemical analyses of MurT interacting OBJECTIVE partners reveal GatD (Rv3713) as a protein To validate the PG recycling and amidation partner of MurT for the formation of the enzyme, MurT, as a novel drug target for MurT-GatD complex required for PG TB treatment. biosynthesis. GatD-mRFP was found to co- localise with MurT. Cells depleted of MurT METHODS were found to be highly sensitive to cell Bioinformatics techniques were used wall targeting antibiotics. to identify Mtb genes required for PG recycling. The enzyme MurT (Rv3712) was CONCLUSION selected for further study. Allele exchange Our observations suggest that PG mutagenesis was used to generate MurT amidation plays a decisive role in the mutant in M. smegmatis and CRISPR-cas9 polymerisation of PG in mycobacteria and gene silencing was used to create MurT highlight the MurT-GatD complex as a mutants in Mtb. Confocal microscopy novel drug target. coupled with PG labelling fluorescent substrates were used to study the growth

83 NATIONAL HEALTH SCHOLARSHIP PROGRAMME (NHSP)

MS PUMLA ZONKE – PROGRAMME ADMINISTRATOR

84 SUPERVISION SYSTEM OF WBOT IN NORTH WEST PROVINCE DISTRICTS 1T. Assegaai, 1H. Schneider 1 School of Public Health, University of the Western Cape, Bellville

BACKGROUND interviews and focus group discussions. The ward-based outreach teams (WBOT) We elicited perceptions on supervision of programme constitutes South Africa’s WBOT and mapped social and professional national community health worker (CHW) networks between WBOT members and programme. Many challenges that CHWs PHC staff. Key informants included WBOT, face, point to the need for supervision operational managers and middle-level systems that not only monitor performance managers. but also provide moral and other forms of support. RESULTS Policy and training documents outline a line OBJECTIVES of authority between WBOT members and To develop a supportive supervision facility staff. However, details and specifics framework that will contribute to of supervision are limited. Preliminary effective strategies which improve the analysis shows that team leaders are critical implementation of supportive supervision role players and provide lots of support processes of national CHW programmes. to WBOT members, and their role seems For this phase of the study, we describe to correlate with the document review the extent to which policy and training results. Data show that WBOT members documents relating to WBOT provide communicate and support each other. guidance on supervision processes and However, facility staff do not appear to explore interactions among team members have regular or close interactions with and the primary health care (PHC) staff. WBOT members.

METHODS CONCLUSIONS This qualitative study included a document Weaknesses in the current supervision review and in-depth interviews. We system of WBOT exist. Adequate provision reviewed policy and training documents of support and supervision guided by of the National Department of Health formal instructions, dedicated human focusing on text relating to the supervision resources and training are key to the system of the WBOT programme. In the performance and sustainability of scaled- Ngaka Modiri Molema District, we used up CHW programmes. a semi-structured interview guide with open-ended questions in one-on-one

85 DIVERSITY AND ECOLOGY OF ASTROVIRUSES IN SOUTH AFRICAN BATS 1K. Barnard, 1N. Ithete, 1W. Preiser, 2S. Schultz-Cherry 1 Faculty of Medicine and Health Sciences, Department pathology, Division Medical Virology, Stellenbosch University; 2 Department of Infectious Disease, St. Jude Children’s Research Hospital, Memphis, United States of America

BACKGROUND RESULTS In the search for wildlife hosts of potential Phylogenetic analyses of the SAn bat zoonotic diseases, bats (Chiroptera) astrovirus RdRp sequences (n=44) suggest were found to play an important role as that clustering is not always according reservoirs. Astroviruses (AstVs) are among to species or geographical location. The a wide variety hosted by bats. AstVs are ML tree of the ORF2 sequences indicates transmitted via faecal-oral route and cause that the SAn bat AstV sequence shares a acute gastroenteritis and in rare cases common ancestor with human astrovirus encephalitis and hepatitis. Little is known isolates from China. This could be because about AstVs occurring in southern African there are not many ORF2 bat sequences (SAn) bats. available for analysis. The generation of additional sequences should improve OBJECTIVES confidence in phylogenetic inference of To investigate the diversity and ecology bat AstVs. qPCR results indicated that of SAn bat AstVs using molecular-, amplification of AstVs in a bat colony phylogenetic- and statistical modelling peaked after the recolonization of the techniques. roost. The qPCR assay detected 20% more positive samples than the conventional METHODS screening PCR, indicating its value as a Bat faecal samples (n=600) were screened screening tool for bat AstVs. Statistical for the presence of AstVs using a screening analyses indicated that species identity, sex assay that targets the RNA-dependent RNA and biome influenced astrovirus positivity. polymerase (RdRp) gene. Based on the RdRp sequences a real-time PCR (qPCR) assay CONCLUSION was developed and used to monitor the AstVs in SAn bats are highly diverse and amplification of AstVs in a bat colony over could potentially be zoonotic based on the time. The qPCR assay and the conventional phylogenetic analyses of the capsid protein screening assay were compared to each gene. other regarding detection. Phylogenetic analyses were carried out using MEGA v7 and Geneious R12.

86 MATERNAL EXPOSURE TO TRAUMA AND CHILD ADVERSE GROWTH OUTCOMES IN A SOUTH AFRICAN BIRTH COHORT 1W. Barnett, 2S. Halligan, 1H.J. Zar, 3K.A. Donald, 4,5D.J. Stein 1 Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, and Medical Research Council Unit on Child & Adolescent Health, University of Cape Town (UCT), South Africa; 2 Department of Psychology, Bath University, United Kingdom; 3 Division of Developmental Paediatrics, Department of Paediatrics & Child Health, Red Cross War Memorial Children’s Hospital, UCT, South Africa; 4 Department of Psychiatry and Mental Health, UCT, South Africa; 5 South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa

BACKGROUND growth (weight, height, stunting, wasting) Mothers and children in low- and middle- were investigated using multinomial and income settings such as South Africa are at logistic regression. Maternal mental health risk of exposure to high, sustained levels outcomes were examined as possible of violence and trauma, with potentially mediating variables. negative health consequences for exposed children. However, there is limited data RESULTS on the impact of maternal trauma on At age 12 months, the prevalence of child growth that derives from high-risk stunting and wasting in 863 children was communities. 18% and 4%, respectively. High levels of maternal childhood trauma (35%) OBJECTIVE and IPV (28%) were also present in the We aimed to investigate the impact of cohort. Results indicate an association pre-existing maternal childhood trauma, between IPV exposure and pre-existing and maternal exposure to intimate partner maternal childhood trauma, and child violence (IPV) in the perinatal and early stunting through age two years. Maternal post-partum period and adverse growth in depression mediated this relationship. children through age two years. CONCLUSION METHODS In high-risk communities such as South This study was nested in the Drakenstein Africa, it is critical to gain an improved Child Health Study, a longitudinal birth understanding of pathways by which cohort. Maternal IPV (emotional, physical maternal trauma affects child growth. and sexual) was measured at six time points Maternal mental health problems may from pregnancy to two years postpartum represent an important pathway by which and maternal childhood trauma at child growth is compromised. enrolment. Associations between maternal maltreatment in childhood and IPV and child

87 BIOMECHANICAL ANALYSIS OF SPECIFIC MOTOR IMPAIRMENTS CONTRIBUTING TO EARLY FUNCTIONAL DECLINE IN ADULTS LIVING WITH HIV/AIDS: SUB-STUDY TO THE CAPE WINELANDS HAART TO HEART/ENDOAFRICA STUDY 1K. Berner, 1L. Morris, 1Q. Louw 1 Division of Physiotherapy, Department of Health & Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa

BACKGROUND recorded, and self-reported function and The prevalence of locomotor impairments fall-history. These data will be correlated to remains concerning among people investigate associations. living with HIV/AIDS (PLWHIV), despite advanced antiretroviral therapies. A poor RESULTS understanding exists of how gait and The systematic review revealed that balance are quantitively affected in PLWHIV. objective locomotor impairments exist in PLWHIV, resembling fall-associated OBJECTIVES parameters in the elderly. Findings from To provide quantitative biomechanical Study One of psychometric testing information about locomotor impairments using healthy volunteers indicated that of PLWHIV, and to correlate clinical test the PIMCS’s output was not directly performance to 3D-motion analysis, self- comparable to the reference standard, but reported function, and falls. good repeatability and high correlation to CGM-based models implied that PIMCS METHODS gait data are comparable when using the Phase I included a systematic review same system. Following completion of describing objective locomotor data analysis, findings from Study Two will impairments in PLWHIV. This was followed extend these results using a community by two primary agreement, correlation sample of PLWHIV and controls; aiding and repeated-measures studies, aimed interpretation of PIMCS data in a clinical at ascertaining concurrent validity (versus population. Findings from Phase II will optical motion capture) and repeatability answer the overall project aim. Data of gait-measurements using a portable analysis is ongoing. inertial motion capture system (PIMCS) in healthy volunteers, community controls CONCLUSIONS and PLWHIV. Phase II comprised a The project is the first to describe cross-sectional study with an analytical 3D-locomotor biomechanics in PLWHIV. component. The PIMCS was implemented The comprehensive dataset will allow in a clinical setting to measure 3D gait and identification of appropriate clinical test(s) balance biomechanics of 50 PLWHIV and for early community-level screening of 50 seronegative participants. Timed clinical functional decline in PLWHIV. functional test performance was also

88 PATTERNS AND PREDICTORS OF HIV-STATUS DISCLOSURE AMONG PREGNANT WOMEN IN SOUTH AFRICA: DIMENSIONS OF DISCLOSURE AND INFLUENCE OF SOCIAL AND ECONOMIC CIRCUMSTANCES 1K. Brittain, 2C.A. Mellins, 2R.H. Remien, 1T. Phillips, 3A. Zerbe, 3,4E.J. Abrams, 1L. Myer 1 Division of Epidemiology & Biostatistics and Centre for Infectious Disease Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, South Africa; 2 HIV Center for Clinical & Behavioral Studies, New York State Psychiatric Institute, Columbia University, USA; 3 ICAP, Columbia University, Mailman School of Public Health, USA; 4 College of Physicians & Surgeons, Columbia University, USA

BACKGROUND pregnancy and who were initiating ART. HIV-status disclosure may improve psychosocial health and adherence to RESULTS antiretroviral therapy (ART), but existing Among 995 women diagnosed HIV- insights suffer from methodological positive before the pregnancy and entering limitations. antenatal care, 95% had disclosed to ≥1 individual. In Mokken scale analysis, we OBJECTIVE observed two separate dimensions of We explored disclosure over time during disclosure: disclosure to a male partner, pregnancy and postpartum among 1347 and disclosure to family/community HIV-positive women in Cape Town. members. Among 352 women diagnosed during the pregnancy and initiating ART, METHODS 61% disclosed to a male partner and HIV-positive women who were entering 71% to a family/community member by antenatal care were recruited into the 12 months after diagnosis. Among both MCH-ART study. Women who were previously- and newly-diagnosed women, initiating ART were followed until their married/cohabiting relationship status was first postpartum clinic visit, with follow-up associated with increased disclosure to a through 12 months postpartum among male partner, but less to family/community women who chose to breastfeed. We used members. Among newly-diagnosed different analytic methods across three women, relationship status modified the analytic populations to explore disclosure impact of pregnancy intentions and poverty over time: (i) a cross-sectional analysis of on disclosure to a male partner. disclosure reported at entry into antenatal care among all women who were known CONCLUSION HIV-positive before the pregnancy; (ii) a These unique data provide important descriptive analysis of longitudinal data insights into dimensions of disclosure through 12 months postpartum among during pregnancy and postpartum, and women who were known HIV-positive suggest that women’s social and economic and who were initiating ART; and (iii) an circumstances are central determinants of analysis of longitudinal data through 12 disclosure. months postpartum among women who were diagnosed HIV-positive during the

89 UNDERSTANDING TREATMENT INDIVIDUALISATION AND ITS IMPACT ON STUDY DESIGN AND ANALYSIS 1B.S. Carpenter 1 Traditional Medicine Laboratory, University of KwaZulu-Natal; South African Medical Research Council, South Africa

BACKGROUND databases, Academic Search Complete, Evidence exists that certain medications AHFS Consumer Medication Information, and treatments are substantially more CINAHL, Health Source - Consumer efficient for specific subgroups of the Edition, Health Source: Nursing/Academic population. As such, there is an increasing Edition, MasterFILE Premier, MEDLINE, trend within the medical world toward PsycARTICLES, and PsycINFO. personalised and adaptive treatments for a variety of diseases and disorders. However, RESULTS innovations in this area are scattered across We retrieved and reviewed 4702 papers disciplines and need to be adopted more using EBSCOhost. During the review widely. process, 81% of the studies were deemed to be ineligible and a further 6% were OBJECTIVES inaccessible. A wide variety of different To explore how different disciplines designs were used in those articles we undertaking intervention research accepted, with the randomised controlled understand and define individualisation, trial and case-control being the most and to determine what approaches are popular designs for use with individualised used to account for individualisation within treatment. The most common approach to intervention research. individualisation was the use of panomics.

METHODS CONCLUSIONS We conducted a systematic review of In this review, we identify the different the literature focusing on the designs designs and analyses that are currently and analyses used to account for being used to facilitate intervention research individualisation. A variety of synonyms which makes use of individualisation. The relating to individualisation were used innovations seen across the wide variety to identify eligible studies, and only of studies covered by this review will help intervention research was included. prospective researchers to design future The search was conducted between research more proficiently. January 2017 and June 2018 using the

90 “CODEINE IS MY HELPER”: MISUSE OF AND DEPENDENCE ON CODEINE-CONTAINING MEDICINES IN SOUTH AFRICA 1S. Dada, 2M. van Hout, 1E. Rich, 2M. Bergin 1 Alcohol Tobacco and Other Drug Research Unit, South African Medical Research Council; 2 School of Health Sciences, Waterford Institute of Technology

BACKGROUND emerged, with two additional high levels of Misuse of codeine-containing medicines is abstraction. an emerging global public health concern. Most research has been conducted RESULTS in developed countries (i.e. European Findings are illustrated: participant profile Members States, Australia, the United and product preferences, motives for use, States). transitioning to misuse and dependence, pharmacy purchasing and alternative OBJECTIVES sourcing routes, effects and withdrawal To gain an understanding of unique experiences, help-seeking and treatment individual and collective experiences experiences, and strategies for prevention. of trajectories of codeine misuse and dependence in South Africa. CONCLUSION In this study, the need for continued METHODS support for enhanced patient awareness In-depth interviews were conducted with a of the risk of habit-forming use and related purposive sample of adult codeine misusers health consequences and professional and dependents (n=25). Narratives pharmacovigilance is underscored. were analysed using the empirical phenomenological psychological five-step method. Nine themes with 63 categories

91 INTRODUCING AN ARTERIOVENOUS FISTULA PRE-CANNULATION ASSESSMENT CARE-BUNDLE TO REDUCE COMPLICATIONS IN PATIENTS WITH AN ARTERIOVENOUS FISTULA ON HAEMODIALYSIS 1A. Damons, 1A.S. van der Merwe, 1M.R. Moosa 1 Department of Nursing and Midwifery, Faculty of Medicine & Health Sciences, Stellenbosch University, Tygerberg

BACKGROUND care-bundle (intervention) within a The prevalence of diabetes in sub-Saharan haemodialysis Unit in the Western Cape. countries is a specific concern, with 9.4 million people living with diabetes in METHODS Africa, which is expected to increase to This study fits the intervention research 12.7 million by 2025. Thus, an estimated model and follows the first four of the six 6–16% of the sub-Saharan population will phases of intervention as described by be diagnosed with diabetic nephropathy Rothman and Thomas in 1994. Descriptive resulting in end-stage kidney disease and inferential statistical analysis will be (ESKD) and requiring renal replacement performed. therapy. In South Africa, for a patient to gain RESULTS access to treatment on a renal replacement The study has been approved by the ethics programme, a selection committee committee of Stellenbosch University reviews each case. Patients diagnosed (project reference number #0552; ethics with ESKD receiving dialysis therapy are ref.no. #S17/07/112). Data collection is at an increased risk of infection because currently in progress and will hopefully be of open vascular access, which is regarded completed in January 2019. as their lifeline during dialysis therapy. The early detection of arteriovenous fistulae CONCLUSION (AVF) complications can benefit the patient By detecting infection from the AVF very because of early diagnosis and treatment. early or determining the incidence of Therefore, it is critically important for complications relating to AVF failure and staff working in dialysis units to detect infection, we anticipate reducing these AVF complications before initiation of complications in patients on haemodialysis haemodialysis to prevent infection which in the long-term. may lead to death or prolonged stay in hospitals.

OBJECTIVES To design, develop and pilot-test a prototype AVF pre-cannulation assessment

92 SUSTAINABLE FINANCING OPTIONS FOR MENTAL HEALTH CARE IN SOUTH AFRICA: FINDINGS FROM A SITUATION ANALYSIS AND KEY INFORMANT INTERVIEWS 1S. Docrat, 2C. Lund, 3D. Chisholm 1 Alan J. Flisher Centre for Public Mental Health, Department of Psychiatry and Mental Health, University of Cape Town, South Africa; 2 Centre for Global Mental Health, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, United Kingdom; 3 Department of Mental Health and Substance Abuse, World Health Organization, Switzerland

BACKGROUND the National Health Insurance (NHI), there is With the implicit neglect for the integration clear evidence of discordance between the of mental health services into general health MHPF and the NHI. The most promising service development in South Africa, there strategies for sustainable mental health is an urgent need for an understanding of financing include increased decentralisation the ways in which existing reforms may be of resources to primary and community leveraged to incorporate the objectives mental health services, active integration of the National Mental Health Policy of mental health into ongoing NHI Framework and Strategic Plan (MHPF) and implementation including expanding the the mechanisms by which these reforms mandate of District hospitals and drawing can be structured and financed in the on the private sector, submission of costed context of fiscal constraint. budget bids to support a mental health conditional grant, and ensuring that explicit OBJECTIVE outcomes and deliverables are in place to To provide recommendations for how monitor Provincial implementation. In the scaled-up mental health services can best longer-term, the NHI benefit package must be paid for within the fiscal constraints and be expanded to include comprehensive structures of the country. mental health services at all levels.

METHODS CONCLUSIONS We conducted a situational analysis guided In this paper, several ways in which existing by a newly developed analytical framework reforms may be leveraged to incorporate the for sustainable mental health financing. objectives of the MHPF and achieve better The review was followed by qualitative, mental health outcomes for South Africans in-depth interviews with a range of expert are suggested. Critical opportunities for national stakeholders. financing mental health service scale-up are revealed to be embedded into South RESULTS Africa’s future health delivery strategy. Although the MHPF is said to be consistent with ongoing efforts toward implementing

93 MULTISYSTEM IMPAIRMENT IN PERINATALLY HIV-INFECTED SOUTH AFRICAN ADOLESCENTS ON ART 1,2L. Frigati, 3K. Brown, 1S. Mahtab, 1L. Zuhlke, 1D. Gray, 1L. Githinji, 4J. Hoare, 2M. Cotton, 3,5L. Myer, 1,6H. Zar 1 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town (UCT), Cape Town; 2 Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Stellenbosch; 3 Division of Epidemiology and Biostatistics, School of Public Health & Family Medicine, UCT, Cape Town; 4 Department of Psychiatry, UCT, Cape Town; 5 Centre for Infectious Disease Epidemiology and Research, School of Public Health & Family Medicine, UCT, Cape Town; 6 Medical Research Council Unit on Child & Adolescent Health, UCT, Cape Town

BACKGROUND RESULTS Perinatally HIV-infected (PHIV+) adolescents Of the adolescents included, 406 were are at risk of chronic disease. There are little HIV+ and 95 HIV- (mean age,12 years; data on multisystem involvement in this 49% female). The median age of ART group, especially in Africa. initiation was 4.2 years (IQR: 1.7-7.8), the median CD4 count was 710 (IQR:564- OBJECTIVE 951) with 63% of HIV+ being virologically To investigate the overlapping burden of suppressed at enrolment. Almost half neurocognitive, cardiovascular, respiratory (45%) the HIV+ cohort had a single-system or renal impairment in the Cape Town impairment, while 134 (33%) had > two Antiretroviral Cohort (CTAAC). systems involved. Of these 30 (7%) PHIV+ had three or four systems involved. Single- METHODS system impairment was as follows, cardiac PHIV+ aged 9–14 years on ART for six 40%, renal 0.1%, neurocognitive 35% and months were recruited from seven sites respiratory 25%. Of those with dual-system across Cape Town, with age-matched morbidity, (n=104), the most common HIV-negative adolescents. Impairment pattern was cardiac and neurological was assessed at enrolment included: (n=43, 52%). There was no difference in Neurocognitive defined as an International viral suppression at enrolment or duration HIV Dementia Scale score <10; cardiac of ART regimen in those with dual- or multi- based on echocardiogram; respiratory system impairment versus either single- or based on spirometry and renal defined no system impairment (p=0.22 and p=0.43, as abnormal glomerular filtration rate. respectively). Single-, dual- or multi-system impairment was defined as having impairment of one, CONCLUSION two or three or more of the four systems Despite relatively early ART initiation measured, respectively. Baseline variables some adolescents will still have significant were compared between groups using systemic morbidity that will require t-tests, Wilcoxon, and Chi-square tests. increasing clinical attention through adulthood.

94 IN VIVO AND IN VITRO STUDIES TO INVESTIGATE THE ROLE OF AUTOPHAGY IN HUMAN TUBERCULOSIS 1P. Gina, 1M. Davids, 1A. Pooran, 1K. Dheda 1 Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa

BACKGROUND recurrent TB. Expression of LC3II protein, Mycobacterium tuberculosis (M.tb) the marker of autophagy from peripheral is one of the world’s most successful blood monocyte cells, monocyte-derived human pathogens that has infected ~2 macrophages and BAL cells were quantified billion people worldwide. The success of by western blot and confocal microscopy. M.tb rests upon its ability to manipulate Cell cultures were treated in vitro with MET, intracellular membrane trafficking events in nitazoxanide and starvation media in the host macrophages and blocking maturation presence or absence of bafilomycin. Some of the phagosome. New therapeutic of the participants received bronchoscopic- interventions for tuberculosis (TB) are instilled BCG with follow-up bronchoscopy urgently required. Whether the induction at day three; autophagic proteins (LC3II) of autophagy by metformin (MET) and were measured pre- and post-treatment in nitazoxanide can promote M.tb stasis the presence and absence of bafilomycin. remains unclear. RESULTS OBJECTIVE MET was a potent inducer of autophagy To determine whether the induction of in BAL cells (p=0.004 compared to no autophagy will facilitate M.tb stasis/killing MET n=16). In vivo, BCG was an inducer in human alveolar and monocyte-derived of autophagy (p=0.018 compared to saline macrophages from persons with varying control n=6). degrees of susceptibility to TB. CONCLUSIONS METHODS These preliminary results demonstrate that Blood and or broncho-alveolar lavage MET and BCG induced autophagy in alveolar (BAL) fluid were obtained from participants cells. These findings have implications for with varying degrees of M.tb susceptibility, new host-directed therapies. The next step presumed latent TB infection, presumed is to determine if the relevant pathways sterilising immunity, previous TB, and influence mycobacterial survival in vitro.

95 SIMULATION AND MODELLING OF LONGITUDINAL HIV VIRAL LOAD MEASURES DURING PREGNANCY AND BREASTFEEDING 1T. Glass, 1L. Myer, 2J. Raboud 1M. Lesosky 1 Division of Epidemiology and Biostatistics, University of Cape Town, Cape Town; 2 Toronto General Hospital Research Institute, University Health Network, Toronto, Canada

BACKGROUND compared, to determine the optimal timing Despite the achievements made in and frequency of VL monitoring. the prevention-of-mother-to-child- transmission, it remains a public health RESULTS concern, especially in sub-Saharan Africa Preliminary results, averaged across runs, where most of the transmissions occur. showed that the percentage of women with The number of children infected with HIV VL <1000 copies/mL at the time of delivery globally has decreased from 290 000 in was 89% (SD, 0.3%), and median (IQR) 2010 to an estimated 150 000 in 2015. time on ART at delivery was 18 weeks (12, While the rapid increase in access to 23). Furthermore, when monitoring based lifelong antiretroviral therapy (ART) for on time since ART initiation, the optimal pregnant and breastfeeding women has led timing for a single VL appeared to be VL to major improvements, there remain gaps measured at 20 weeks after ART initiation in understanding the challenges related (SE: 42%, SP: 99%). However, only 50% of to ART adherence, access in care and women would be eligible for this measure how viral load (VL) monitoring can impact (the remainder having delivered by this mother-to-child-transmission (MTCT). time point). In addition, when monitoring based on gestational age, the optimal time OBJECTIVE point appeared to be testing at 36 weeks’ To determine the optimal VL monitoring gestation with approximately 90% of strategy among pregnant and women eligible to be tested and relatively breastfeeding women. high sensitivity (72%) and specificity (95%).

METHODS CONCLUSIONS A Monte Carlo simulation model of VL Statistical simulation is a useful method trajectories and MTCT risk during the for evaluation of routine monitoring of antenatal and postpartum periods is in longitudinal biomarker data. However, the process of being developed. A wide further work is needed. variety of VL monitoring strategies will be

96 WELL-BEING AMONG YOUTH LIVING WITH AND WITHOUT HIV IN SOUTH AFRICA: A HEALTH ECONOMIC PERSPECTIVE 1D. Govindasamy, 1C. Mathews 1 Health Systems Research Unit, South African Medical Research Council, Tygerberg

BACKGROUND to examine the effects of antiretroviral Recently, well-being has been strongly therapy expansion policies on the well- recommended as an outcome measure for being of youth in South Africa. public policy evaluations as it is considered to capture wider societal benefits. However, RESULTS little is known on which well-being Currently, I have completed data collection measures would be applicable for public for my review and qualitative study. health policy evaluation in sub-Saharan Preliminary data analysis suggests that African, particularly policies targeting youth well-being among youth in this setting is such as HIV/AIDS treatment policies. defined in terms of context, and is shaped by cultural values, including societal and OBJECTIVE gender norms. Moreover, key drivers of To contribute to the understanding of well-being include educational attainment, well-being measurement for HIV-policy employment, social support, hope, access evaluation among youth (15–24 years) in to basic services. South Africa. CONCLUSIONS METHODS Over the next year and a half, analyses The overarching PhD study design is and write-up papers will proceed and be mixed-methods (sequential exploratory) submitted to appropriate journals and and comprises three papers. 1) A mixed- presented at conferences. Moreover, a methods review to understand the community engagement session, which predictors and experiences of well-being will entail sharing findings with healthcare among youth living with HIV in sub-Saharan workers and youth at the study clinics will Africa; 2) A qualitative study in which we be conducted. The findings from my papers seek to understand the perceptions and and community engagement session I will experiences of well-being via focus-group share via a policy brief to the Department discussion and in-depth interviews with of Health, which will outline key areas for youth in Umlazi, KwaZulu-Natal, South programme intervention to improve well- Africa; and 3) A quasi-experimental analysis being among youth in South Africa.

97 KNOWLEDGE, ATTITUDES AND PRACTICES ON SCHISTOSOMIASIS IN SUB-SAHARAN AFRICA: A SYSTEMATIC REVIEW 1H. Gwebu Sacolo, 1M. Chimbari, 1C. Kalinda 1 School of Nursing and Public Health, College of Health Sciences, Howard College Campus, University of KwaZulu-Natal, Durban, South Africa

BACKGROUND RESULTS The World Health Organization emphasises Studies that we reviewed reflected the use of integrative approaches in inadequate knowledge, attitudes and controlling and eliminating schistosomiasis. practices in relation to schistosomiasis. A detailed understanding of socio-cultural Age, gender, occupation, and level of factors that may influence the uptake of education showed to have an extensive the intended health activities and services impact on schistosomiasis knowledge and is vital. practices. About 60% of these studies revealed widespread misconceptions OBJECTIVES on the transmission and prevention of In our study, we sought to understand the schistosomiasis. The disease was mostly knowledge, attitudes, perceptions, beliefs believed to be caused by HIV, consuming and practices about schistosomiasis in unclean water and contaminated food. various sub-Saharan Africa communities. Risky water-related practices, such as swimming, bathing and washing clothes METHODS in open water bodies were identified as A systematic search of literature dating key factors promoting transmission of the from 2006–2016 was done using Medline, disease. PubMed, CINAHL, Psych info and Google Scholar databases. The keywords entered CONCLUSION were, “Schistosomiasis, S. mansoni, S. A comprehensive health education haematobium, knowledge, attitudes, programme using contextual and perceptions, beliefs and practices in standardised training tools may improve sub-Saharan Africa” in combination with peoples’ knowledge, attitudes and Boolean operators (OR, AND). In this practices in relation to schistosomiasis context, we reviewed studies conducted prevention and control. among school children, community members, and caregivers of preschool children.

98 FACTORS INFLUENCING HIGH SCHOOL RE-ENTRY AND SCHOOL PARTICIPATION FOLLOWING THE ONSET OF A TRAUMATIC BRAIN INJURY 1L. Jacobs-Nzuzi Khuabi 1 Division of Health and Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University

BACKGROUND RESULTS For an adolescent, school participation is Enablers to school re-entry and school one of the primary occupations that may participation included the engagement be disrupted by post-traumatic brain injury in the valued occupation of school, the (TBI). Post TBI, the adolescent has to deal use of strategies, personal attributes and with the expected associated adjustments external supports which increased the of their development stage, along with adolescents’ capacity to adapt. The main adjusting to a range of impairments and barriers included changes in abilities, increased dependence resulting from skills and role fulfilment post TBI, a lack the TBI. This combined with contextual of open communication between team factors may have implications for their members, human and financial constraints, preparedness to re-enter and participate in a lack of preparation of the adolescent and school post TBI. their contexts, inaccessibility (structural, attitudinal and lack of safety) as well as a lack OBJECTIVE of psychological support to adolescents To gain an increased understanding of the and their families. enablers and barriers to high school re- entry and school participation post TBI. CONCLUSIONS In conclusion, we found that school re-entry METHODS requires preparation of adolescents and This qualitative study used a multi-case study their contexts. Planning should encompass design, which included documentation the adolescent’s full school experience, review, semi-structured observations and i.e. preparing to go back to school, being semi-structured interviews with eight back at school, grade-grade transition and adolescent learners and each of their moving on from high school. The learning primary caregivers, teachers and principals. support should be flexible and requires ongoing monitoring to ensure that support remains relevant and responsive to the learner’s changing needs. Adolescent learners and their primary caregivers need to be active partners in identifying and planning for the learner’s support needs.

99 DENDRITIC CELLS AND OTHER ANTIGEN PRESENTING CELLS INDUCE PROTECTIVE TH1 IMMUNITY IN MICE INFECTED WITH CENTRAL NERVOUS SYSTEM TUBERCULOSIS 1K. Kgoadi, 1R. Keeton, 1N. Hsu, 1A. Walters, 1-3M. Jacobs 1 Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Pathology Department, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; 2 National Health Laboratory Services, Johannesburg, South Africa, 3 South African Medical Research Council, Cape Town, South Africa

BACKGROUND and single cell suspensions were also Tuberculosis (TB) is primarily a pulmonary generated for determining immune cell infection caused by Mycobacterium recruitment kinetics, phenotype and tuberculosis (Mtb) affecting one-quarter of functional profile using flow cytometric the global population. Approximately 1% of analysis. extra-pulmonary TB cases are attributed to central nervous system tuberculosis (CNS- RESULTS TB), a severe form of TB associated with high Acid-fast bacilli were detected in the brain morbidity and mortality mainly occurring in ventricles, and inflammatory responses children and immunocompromised adults. occurred post infection. There was a CNS-TB faces diagnosis and treatment significant decrease in the bacterial burdens challenges. Pathogenesis of CNS-TB is four weeks after infection. Activated APCs initiated as a secondary infection during (microglia, dendritic cells and infiltrating the haematogenous dissemination macrophages) produced high amounts of pulmonary infection to the brain. of IL-1beta, a pro-inflammatory cytokine Mechanisms and specific cell types targeted associated with protection against Mtb. by Mtb to evade the BBB remain primarily The T cells that infiltrated the brain undefined. Dendritic cells are professional displayed a Th1 Phenotype evident by the antigen presenting cells (APCs) which have high expression of transcription factor T-bet been neglected in CNS-TB research. and high levels of secreted IFN-gamma. T cells infiltrating the brain consisted of high OBJECTIVE amounts of activated CD4+ T cells and less To characterise APCs and T cells that CD8+ T cells. infiltrate the brain post-Mtb infection. CONCLUSION Mtb METHODS Functional phenotype of infected C57BL/6 mice were intracerebrally infected DCs favours Th1 immunity and together with H37Rv (Mtb) and saline mock-infected. with microglia/macrophages are promising Mice were sacrificed on day one, week drivers of protective immunity against CNS- two, four and six and brains harvested for TB making them target cells for strategic experimental analysis. Histopathological therapeutic intervention. analysis was performed on brain sections,

100 BECOMING AN INTERVENTIONIST-RESEARCHER DURING THE RESEARCH PROCESS 1H. Koch, 2M. Pillay 1 Occupational Therapy, University of KwaZulu-Natal (UKZN), Durban; 2 Audiology, UKZN, Durban

BACKGROUND RESULTS During research with humans, it is important The four themes identified include “I’m that they remain protected throughout the confused”, “Dependency”, “I feel like I’m process. The ethics application is even alive again” and “You didn’t do anything, more rigorous when dealing with vulnerable don’t come back”. The complexity that populations. However, whether some kind arises in various situations, and how of intervention occurs during or after the sometimes there is a catapulting effect, and research study, depends on various factors, ‘no turning back’ is demonstrated. i.e. the methodology chosen. This presents a conundrum for the researcher, when the CONCLUSIONS participants are food insecure, in danger, or These potential, seemingly conflicting have an illness and the initial methodology interventions regarding the problems chosen does not reflect intervention. that participants experience present an irreconcilable difference for the researcher. OBJECTIVE There is no clear-cut answer to what the To evaluate the data collection process correct and best steps would be to take, in which the research methodology for a since each one could significantly alter food insecurity study expanded from life the story of the participant including the history research to including interventionist relationship between the researcher and research methodology. the participant. Since life history research involves co-construction of stories, it seems METHODS understandable that any kind of presence In this qualitative study the reflective within the participants’ lives, can cause an journals of the researcher and research altering of their life course and vice versa. assistant were analysed from the data Each encounter is unique and thus it is not collection process of the main study. These possible to predict ahead of time which typed notes were inputted into Nvivo 11, would be the best course of action. following which thematic analysis occurred.

101 3D SCAFFOLD FOR NEURAL TISSUE ENGINEERING 1G. Mahumane, 1P. Kumar, 1Y. Choonara, 1V. Pillay 1 Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Science, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

BACKGROUND cryogel showed a slower decomposition Mounting literature has shown the rate compared to the uncrosslinked cryogel, potential of scaffolds for neural repair. an indicator that crosslinking increased the However, many of these scaffolds are in the thermal stability of the cryogel. Cryogels experimental phase and have yet to yield were sponge-like and exhibited fast functional repair at a clinical level. swelling (within 1-2 seconds). The scaffold exhibited an increase in volume following OBJECTIVE hydration while maintaining its shape, as To obtain an injectable hybrid scaffold evidenced by stereomicroscopy. Scanning presenting multiple cues to augment tissue electron microscopy (SEM) revealed that regeneration through interconnected the microstructure of the cryogel comprises pores, fibres for the guidance of cell growth interconnected pores, ranging from 22-192 and a hydrogel filling for the encapsulation µm, separated by a thick pore wall. The of cells in a hydrated environment. electrospun fibres ranged from 500-980 µm, as observed by SEM. METHODS The scaffold is designed to be CONCLUSIONS compressible, enable adherence, provide PC-12 adherent cell line is used as a model multiple mechanical cues to stimulate cell for neuronal differentiation, function and growth, while preserving cell viability and death. Cells grown in serum-containing neural integrity during transplantation via medium exhibit a rounded morphology. the minimally invasive injection route or The morphology of the cells progresses to otherwise. spindle-shaped with dendritic processes once adhered to the culture flask. Thus RESULTS far, cells have been cultured growth The chemical modification via crosslinking medium (Dulbecco’s modified Eagle’s was confirmed by Fourier transform infrared medium, horse serum, foetal bovine serum spectra. Thermogravimetric analysis and antibiotic penicillin/streptomycin) showed an 81% and 69% weight loss in in preparation for seeding into the 3D the un-crosslinked and crosslinked cryogel, scaffold. respectively. The curve of the crosslinked

102 PULMONARY REHABILITATION FOR PEOPLE WITH TUBERCULOSIS IN A HIGH HIV-POSITIVE SETTING: A RANDOMISED CONTROL TRIAL 1S. Manie, 1S.L. Amosun, 2G. Meintjes, 3B. Allwood 1 Department of Health and Rehabilitation Sciences, University of Cape Town (UCT), Cape Town; 2 Department of Medicine, UCT, Cape Town; 3 Department of Medicine, Stellenbosch University, Tygerberg

BACKGROUND is designed to assess the superiority of the Only in the last decade research has shown experimental intervention over standard that tuberculosis (TB) patients present with of care in a randomised controlled trial. chronic obstructive pulmonary disease post Enrolled participants will be randomly successful completion of drug therapy. Even allocated to either the intervention or though pulmonary impairment is evident control group. The intervention group post-TB cure, uptake of these findings into will participate in two-weekly pulmonary clinical practice has been slow. Pulmonary rehabilitation sessions which are exercised- rehabilitation or any other additional care based for 12 weeks. Data pertaining to to address poor lung function or impaired lung function (FEV1, FVC and FEV1/FVC), functional ability arising from decreased functional capacity (three-minute step test) lung function post TB is meagre in the and quality of life questionnaires (EQ-5D South African context. and SGRQ) will be collected at enrolment, halfway through the intervention and on OBJECTIVES completion of the 12 weeks. To assess the effectiveness of the pulmonary rehabilitation programme (PRP) RESULTS on outcomes related to lung function, Data collection still in progress. functional capacity, and quality of life for people receiving TB therapy. CONCLUSION Not applicable. METHODS A pilot randomised, single-blinded, pre- test-post-test design will be used. The trial

103 PHARMACOGENETICS OF TENOFOVIR 1K. Montjane, 1D. Mhandire, 2E. Kampira, 1C. Dandara 1 Division of Human Genetics, Faculty of Health Sciences University of Cape Town, Cape Town, South Africa; 2 Department of Pathology, University of Malawi College of Medicine, Blantyre, Malawi

BACKGROUND responses observed for TDF among African HIV/AIDS is a pandemic disease, with Africa patients. carrying the highest burden. Antiretroviral therapy (ART) used as a combination of at METHODS least three antiretrovirals (ARV) has improved Malawian, Zimbabwean and South African the HIV/AIDS prognosis into a more HIV/AIDS patients (n=450) on TDF will be manageable chronic condition. Tenofovir analysed. We will evaluate all SNPs with (TDF) is used as part of combination ART functional significance in ABC and SLC and in the prevention of HIV. Even using genes associated with TDF transport using this therapy, viral replication and resistance TaqMan Assays, PCR-RFLP, SNaPshot, are still observed, and it is thought a host Sanger sequencing and where possible of pharmacogenetic factors play a role. exome sequence a few samples. The TDF is not metabolised but transported frequencies of these SNPs will be analysed by proteins coded for by polymorphic with different statistical tools to determine genes. Interpatient variability in TDF- their role in TDF response among patients drug disposition has been observed, and and their association with adverse drug genetic factors have been proven to have effects. a role in ARV disposition. Single nucleotide RESULTS polymorphisms (SNPs) have been reported Data analysis in progress. in transporter genes among Caucasian and Asian populations. However, their CONCLUSIONS distribution in African populations is We hope to understand the effect of genetic poorly understood. Therefore, we aim to variation of transporter genes in TDF investigate the role of genetic variation patients in sub-Saharan Africa. Ultimately, in genes coding for transporters on TDF we will reveal if pharmacogenetics can be regimen. used to identify which patients are likely to present with adverse drug effects before OBJECTIVE treatment by recommending relevant To genotype genes that are associated with pharmacogenetic tests. a disposition for variation that may affect

104 DEVELOPING AN EDUCATION PROGRAMME DESIGNED TO IMPROVE QUALITY OF LIFE OF PEOPLE LIVING WITH HIV ON ANTIRETROVIRAL THERAPY IN THE JOHANNESBURG METROPOLE 1,2M. Mutemwa, 2D. Phetlhu 1 Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, South Africa; 2 Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa

BACKGROUND RESULTS The widespread accessibility of Of the 434 participants, 70.5% were antiretroviral therapy (ART) has significantly women, and 29.5% were men. The overall improved the lives of people living with mean age of the participants was 43 years HIV (PLWHIV). However, it has become old (men 45 years vs. women 42-years-old) apparent that we not only focus only on P<0.001. The overall QoL for PLWHIV was the individuals’ survival but on their overall 77% among the participants, with 70% of quality of life (QoL). them showing good psychological health; good physical health was observed to be OBJECTIVE 74%, healthy social relationships 71%, and To develop an education programme that environmental health 65%. seeks to support and improve the QoL for these individuals. CONCLUSIONS According to the findings in this study, METHOD most of the PLWHIV show good QoL in A cross-sectional survey was conducted the different domains investigated. We among 434 adults receiving care for HIV propose that interventions aimed at this infection at three academic hospitals in the population to improve QoL should take Johannesburg Metropole. A quantitative into account the physical, psychological, research approach with a descriptive social, environmental, and other aspects survey design was used. Data were of PLWHIV during treatment, care, and collected through interviewer-reported support. More importantly, there is a need questionnaires and QoL improvement for health interventions such as education linked to PLWHIV on ART was assessed. We programmes, which can further prove to be used a Likert scale questionnaire, and the useful. data were analysed using SPSS Version 24.

105 AN ANALYSIS OF OVERWEIGHT AND OBESITY IN SOUTH AFRICA: THE CASE OF WOMEN OF CHILDBEARING AGE 1M. Nglazi 1 School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town

BACKGROUND METHODS Evidence is lacking concerning the socio- Data will be obtained from publicly economic inequalities in and determinants available data sources. Logistic regression of overweight and obesity among South will be performed to estimate the temporal African women of childbearing age. In this trend in the prevalence of overweight research project, the aim is to analyse and and obesity. A growth model will be interpret national data on the prevalence, used to estimate the average rate of determinants and socio-economic change in body mass index (BMI) over inequality in overweight and or obesity in time and examine the factors associated South African non-pregnant women aged with the different BMI trajectories. The 15–49 years old. concentration index will be used to measure the socio-economic inequality in the health OBJECTIVES variable (i.e. household food spending and To assess 1) the pattern and trends in the consumption, overweight and obesity, and prevalence of overweight and obesity from inter-generational overweight and obesity 1998–2015 in South African women of in this case). childbearing age; 2) the changing pattern in socio-economic inequality in food RESULTS consumption patterns over the period 2005– Unfortunately, the study findings are not 2011 in these women’s households; 3) the yet available. determinants of obesity in these women, with a focus on the specific households’ CONCLUSION food consumption patterns; 4) the changing These findings will be able to contribute to pattern in socio-economic inequality in new knowledge on the ongoing national overweight and obesity over the period efforts towards understanding the socio- 1998–2015 in these women; and 5) the socio- economic inequalities in overweight and economic inequality in inter-generational obesity along with their determinants. overweight and obesity in South Africa.

106 GENOME-WIDE DIFFERENTIALLY METHYLATED GENES ASSOCIATED WITH PTSD IN FEMALE RAPE SURVIVORS 1J. Nothling, 1S. Seedat, 2N. Abrahams, 1S. Hemmings 1 Department of Psychiatry, Stellenbosch University, Stellenbosch; 2 Gender and Health Research Unit, South African Medical Research Council, Tygerberg

BACKGROUND was extracted from peripheral blood and Alterations to the epigenome in response to analysed using the Illumina Epic BeadChip psychological trauma have been reported microarray. Logistic regression models, as a mechanism mediating gene and adjusting for multiple comparisons, were environmental interaction. Differentially used to identify differentially methylated methylated genes involved in the biological genes in participants with and without pathways associated with the adverse PTSD at three months post-rape. phenotypic behavioural presentations in posttraumatic stress disorder (PTSD) RESULTS has previously been identified. However, PTSD status was associated with 423 studies have focussed on differential differentially methylated genomic regions. methylation of single candidate genes in Paired box 8 (PAX8), encompassing eight participants exposed to heterogeneous CpG sites, p=9.14E-20 and Zinc Finger index traumas. Protein 57 (ZFP57), encompassing 19 CpG sites, p=4.84E-18 were among the OBJECTIVE top twenty genomic regions significantly Identify genome-wide differences in associated with PTSD in this dataset and methylation profiles of a group of women previously found to be associated with exposed to rape, with and without PTSD. PTSD in other traumatised cohorts.

METHODS CONCLUSIONS Female isiZulu participants (n=48) between PAX8 may be involved in PTSD symptoms 18 and 40 years old, who reported an related to sleeping difficulties, and ZFP57 is incident of rape within the previous twenty believed to be involved in susceptibility to days, were recruited from three Thuthuzela stress governed by differential methylation Care Centres and a Crisis clinic in Durban, in hippocampal cells. To our knowledge, Kwa-Zulu Natal. Rape-exposed participants this is the first study to investigate the with and without PTSD were matched on genome-wide profiles of women exposed HIV status, age, childhood maltreatment to rape in Africa. Confirmation of these and other lifetime trauma exposure, body findings will require replication in larger mass index and smoking status. DNA cohorts.

107 THE QUALITY OF LIFE OF PRIMARY HEALTH CARE PATIENTS DIAGNOSED WITH HYPERTENSION AND/OR DIABETES IN THE EASTERN CAPE, SOUTH AFRICA 1Z. Ogle, 1,2L. Koen, 1,2D.J.H. Niehaus 1 Medicine and Health Sciences, Stellenbosch University; 2 Stikland Hospital

BACKGROUND RESULTS Hypertension and diabetes have emerged Sixty-nine (87%) females and 10 (13%) as a major medical and public burden males with mean age of 49 (SD=8.6844) and have been associated with a short life participated in the study. More than half expectancy and poor quality of life (QOL). (54%) reported medical conditions other As such, QOL is an important indicator than hypertension and diabetes. There to evaluate hypertension and diabetes were low mean scores on the physical treatment outcomes. health (12.42), psychological health (14.17), and environment (12.71) domains. The OBJECTIVE social relationships domain had the highest To describe the QOL of primary health care mean score (14.97). There was a statistically patients diagnosed with hypertension and/ significant difference in the scores of or diabetes. people with hypertension coexisting with other medical conditions compared to METHODS people without other medical conditions This was a cross-sectional study with 79 (physical domain, 0.01) and (environment participants from five primary health care domain, 0.03). centres in the Eastern Cape, South Africa. Demographic data were summarised as CONCLUSIONS frequencies, percentages, means with In this study, we confrmed that living standard deviation (SD). The Mann-Whitney with hypertension and/or diabetes was U Test compared mean scores between associated with a poor QOL. People with people with and without other medical hypertension comorbid with other medical conditions. conditions had significantly poorer physical and environment QOL compared to those without other medical conditions. This highlights the need for interventions in primary health care to improve the QOL of people living with hypertension and/or diabetes.

108 FINDING FORMER TUBERCULOSIS PATIENTS - A HIGH-RISK GROUP FOR TUBERCULOSIS-ASSOCIATED MORBIDITY AND MORTALITY IN CAPE TOWN, SOUTH AFRICA: A PILOT STUDY 1,2M. Osman, 1R. Brown, 1R. Dunbar, 1G. Hoddinott, 2A. Welte, 1A.C. Hesseling, 1F.M. Marx 1 Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg; 2 South African Centre for Epidemiological Modelling and Analysis, Stellenbosch University, Stellenbosch

BACKGROUND contacted and interviewed. Of the latter, A high risk of tuberculosis (TB), chronic lung the median age was 41 years (IQR 33–49 disease and mortality have been reported years); 63% (32/51) were male and 51% among people with a history of previous (26/51) were HIV-infected. Of 51, 28 TB treatment, but data from high-incidence (55%) reported shortness of breath when settings remain limited. walking fast or uphill, 26 (51%) having to walk slower because of breathlessness, OBJECTIVES 24 (47%) wheezing, and 15 (29%) severe To locate adults who had successfully chest infections in the past year. Of 28 completed TB treatment in the past five participants who provided a sputum years, and to characterise general morbidity sample, one (3.6%) had culture-positive and mortality. TB. Another two reported currently being re-treated for TB, providing 3/51 prevalent METHODS cases of TB. Among 208 individuals unable In this cross-sectional study, we used to be contacted, 15 (7.2%) were confirmed routine electronic TB treatment register to have died. data to randomly select adults (≥18 years) who successfully completed pulmonary CONCLUSIONS TB treatment between 2013 and 2017. In this setting, only 20% of individuals Household visits were conducted in a treated in the past five years could be high-incidence community in suburban located and interviewed. Our results Cape Town to locate and survey former TB are consistent with a high prevalence of patients. Individuals who could produce respiratory disease including active TB sputum were bacteriologically investigated among former TB patients, and higher for TB. Household interviews and vital mortality compared to TB treatment-naïve registration data were used to estimate individuals of similar age. mortality among patients who could not be traced.

RESULTS We sampled 259 former TB patients of whom 51 (20%) were successfully

109 A NOVEL METALLO-ENDOPEPTIDASE REQUIRED FOR PEPTIDOGLYCAN REMODELLING DURING OSMOLARITY CHANGES IN M. TUBERCULOSIS 1A. Papadopoulos, 1B. Kana 1 DST/NRF Centre of Excellence for Biomedical TB Research, Wits University, Johannesburg, South Africa

BACKGROUND RESULTS The persistence of tuberculosis (TB) disease Unexpectedly, deletion of the M. and rising incidence of drug-resistant tuberculosis lytM genes did not cause a cell strains necessitates the discovery of novel separation defect as seen in E. coli and M. therapeutics. An intuitive approach is to smegmatis lytM deletion strains. Instead, target bacterial cell division. The LytM strains of M. smegmatis heterologously family of metallo-endopeptidases regulate expressing M. tuberculosis mepA cell division in model organisms such as exhibited sensitivity to high concentrations Escherichia coli and the non-pathogenic of salt relative to the mepA domain relative of Mycobacterium tuberculosis, expressed. A recent study revealed that M. Mycobacterium smegmatis by activating tuberculosis responds to an increase in salt amidases which degrade the peptidoglycan by remodelling peptidoglycan coinciding cell wall permitting cell separation. Deletion with increased mepA expression. of lytM genes is expected to lead to cell Therefore, mepA is likely required for separation defects. degrading M. tuberculosis peptidoglycan during osmolarity changes. This is being OBJECTIVES investigated further in the M. tuberculosis To characterise the lytM genes of M. mepA-knockout. tuberculosis and validate them as novel drug targets for TB treatment. CONCLUSION Collectively, our data highlight a role for METHODS mepA in adapting to stress conditions Two highly conserved lytM genes, mepA suggesting that this enzyme may be a and nlpAL, were characterised using various useful new drug target for TB. strains of M. tuberculosis including knock- out mutants as well as overexpression and genetically complemented strains, bearing various domains of mepA.

110 HARM-REDUCTION IN THE MANAGEMENT OF ADOLESCENT SELF- HARM: ETHICAL AND PRACTICAL CONSIDERATIONS IN A SOUTH AFRICAN CONTEXT 1S. Pasche, 1J. Bantjes 1 Department of Psychology, Faculty of Arts and Social Sciences, Stellenbosch University

BACKGROUND reduction”, “self-harm serves a function” Self-harm, defined as non-suicidal self- and “meeting the patient where she is”. injury, is globally estimated to occur in 10% of adolescents. The British NICE guidelines RESULTS acknowledge that cessation of self-harm Clinicians regarded self-harm as a coping may be unrealistic for some individuals, and mechanism for patients and questioned that harm-reduction may be appropriate. the expectation of being able to prevent Examples include psychoeducation on it. Anxiety and shame exist around the how to cut without risk of serious injury, implementation of harm-reduction, and how to prevent infection. While because of a fear of colleagues’ reactions. some international health systems have The importance of respecting the employed harm-reduction for self-harm, it patient’s experience and the difficulty in has not been considered in South Africa. distinguishing self-harm with and without intent to die became apparent in the OBJECTIVE narrative. To consider the potential value, pitfalls and ethical dilemmas of using harm-reduction CONCLUSIONS approaches in the psychological treatment While harm-reduction may be an of South African adolescents who self- appropriate strategy in the treatment harm. of self-harm, this practice is not without ethical and practical challenges when used METHODS with adolescents. The appropriateness of We conducted in-depth, semi-structured harm-reduction should be considered on interviews with ten healthcare professionals a case-by-case basis. Possible challenges engaged in the treatment of adolescents include determining intent, the risk of who self-harm, to explore their experiences contagion, and professionals’ anxiety. and ideas for suicide prevention. Interviews Adolescents’ right to autonomy should be were recorded, transcribed and thematically balanced against the individual’s capacity analysed in Atlas.ti. We focus on the theme for decision-making. Clinical guidelines of harm-reduction and associated sub- and combined decision-making by the themes, “the myth of prevention”, “anxiety treating team may reduce anxiety among and shame around implementing harm- health professionals.

111 HIV-ASSOCIATED COGNITIVE DISORDERS IN CHILDREN AND ADOLESCENTS: METHODOLOGICAL INVESTIGATIONS AND VALIDATING A QUICK SCREENING TOOL 1N.J. Phillips 1 Department of Psychiatry and Mental Health, Faculty of Health Science, University of Cape Town

BACKGROUND and inferential statistics were conducted Perinatal HIV-infection has profound using SPSS 25. consequences for cognitive and functional ability of children and adolescents. Context- RESULTS specific assessment tools and methods There were inconsistencies in the literature of cognitive and functional impairment is about which cognitive domains are most lacking. affected by HIV. Findings from the meta- analysis revealed that the cognitive OBJECTIVES domains of executive function and To determine 1) a consensus (if any) in the processing speed are the most affected. literature regarding cognitive effects of the Statistical analysis showed that composite HIV virus in children and adolescents, 2) cognitive domains scores (as opposed a statistically sound method for assessing to global scores) were more accurate in cognitive impairment, 3) the associations detecting HIV-related cognitive differences with cognitive impairment and functional in adolescents. Traditional measures of impairment and the relative risk of having functional impairment were significantly functional impairment in the presence of associated cognitive impairment, and cognitive impairment, and 4) to validate a adolescents had an increased risk of having quick screening tool for risk of cognitive functional impairment if they also had impairment. cognitive impairment. The statistical validity of the youth International HIV Dementia METHODS Scale to screen for risk of cognitive Nested within a larger longitudinal study, impairment in HIV-infected adolescents the Cape Town Adolescent Antiretroviral was demonstrated. Cohort (CTAAC), this quantitative cross-sectional study required specific CONCLUSIONS methodological considerations. For the Traditional assessments/methods may not first, electronic systematic searches were be contextually appropriate in low-income conducted to find relevant literature. settings. The methodological approach These were assessed by two independent and screening tool validated is a start in reviewers, the data extracted and meta- addressing these kinds of issues locally and analysed. For objectives 2–4, data were globally. collected from research participants enrolled in CTAAC. Data scoring, capturing

112 MOUSE MACROPHAGES UPREGULATE MX1 AND MX2 UPON INFECTION WITH MYCOBACTERIA 1R-D. Pietersen, 1G. Leisching, 2C. van Heerden, 1B. Baker 1 NRF/DST Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg; 2 Central Analytical Facility (CAF), DNA Sequencing Unit, Stellenbosch University, Stellenbosch

BACKGROUND RESULTS The disease-causing agent, Mycobacterium The RNA-Seq data showed that very high tuberculosis, survives inside human fold changes occur for the gene expression macrophages. However, non-pathogenic of Mx1 and Mx2 upon infection with mycobacteria do not survive inside healthy mycobacteria and the qPCR results confirm host cells. Comparing the host response this. The pathogenic strains elicit a much between infection with pathogenic and stronger response to these interferon non-pathogenic mycobacteria might reveal (IFN)-induced genes as compared to the important determinants (molecules) that non-pathogenic strains. Mx1 and Mx2 play are involved in the intracellular survival roles in cytokine signalling and antiviral strategy of Mycobacterium tuberculosis. responses. Interestingly, the same IFN- Through RNA-Seq data, we previously induced response that fights viruses can observed that mouse macrophages express inhibit the clearance of mycobacteria. If Mx1 RNA molecules at different levels when and Mx2 promote the intracellular growth comparing infection between pathogenic of mycobacteria, then interfering with the (Mycobacterium tuberculosis H37Rv and role of these genes using small interfering clinical isolate R179) and non-pathogenic RNA (siRNA) could possibly influence the mycobacteria (Mycobacterium smegmatis intracellular survival of mycobacteria. and bovis BCG). CONCLUSIONS OBJECTIVE The qPCR results confirm the validity of To validate the expression levels of Mx1 the RNA-Seq data. Among the many (MX Dynamin Like GTPase 1) and Mx2 molecules that mycobacteria manipulate through quantitative PCR (qPCR). for its intracellular survival, Mx1 and Mx2 could be on the list of molecules that are METHODS important for intracellular survival. Testing Mouse macrophages were infected with for this can be done by knocking down the same strains as used for the RNA- these genes and assessing the intracellular Seq analysis, followed by extraction of health of the mycobacteria. macrophage RNA, conversion to cDNA and determining the relative expression levels through qPCR.

113 DECIPHERING THE PHYSIOLOGICAL STATE OF DRUG RESISTANT MYCOBACTERIUM TUBERCULOSIS STRAINS 1C.M. Pule, 2G.E. Louw, 1R.M. Warren, 1J.M. Mouton, 1P.D. van Helden, 1S.L. Sampson 1 DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, University of Stellenbosch, South Africa; 2 Institute of Infectious Disease and Molecular Medicine, Division of Medical Microbiology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa

BACKGROUND strains. Low-level gene expression changes The rising incidence of drug resistant in kasA and accD6 (K636WT = 2.0; 2.4 and Mycobacterium tuberculosis (M. tb) strains 2.0; 2.4) and K636RIF (2.6; 2.3 and 2.4; 2.2) negatively influences tuberculosis control. was observed, when normalised to 16s Limited data exist on the physiological rRNA and sigA, respectively, in the studied changes of M. tb during treatment. M. tb strains. RNA-seq analysis identified a few differentially expressed genes of tested OBJECTIVE M. tb strains. To assess the physiological changes of M. tb at the transcriptional level during CONCLUSIONS antibiotic treatment. The 0.05 µg/ml INH concentration was validated and chosen sub-lethal INH METHODS treatment of all tested M. tb strains, which Pan-susceptible Beijing clinical isolate was subsequently used for gene expression (K636), K636 rifampicin resistant in vitro analysis experiments. In the presence of mutant and laboratory strain H37Rv were 0.05 µg/ml INH, M. tb growth was inhibited cultured in 7H9 enriched media and on by ≥ 10%. Low-level gene expression 7H11 agar plates, for daily OD600 readings changes observed, is in accordance with the and CFU/ml assessment. Followed by literature. Thus, verifying that our optimal assessing the optimal concentration of INH sub-lethal INH treatment concentration by titration kill-curve. Moreover, total RNA induced gene-expression changes in was extracted and purified (after 24 hours selected M. tb strains. RNA-seq identified INH exposure), for gene expression analysis differentially expressed genes. Our findings by quantitative real-time polymerase chain suggest that the physiological changes of reaction for selected genes (kasA, accD6) the studied M. tb strains were reflected in and RNA sequencing (RNA-seq) analysis. the total transcriptome. RESULTS The 0.05 µg/ml INH concentration was selected for antibiotic treatment for M. tb

114 HIGH EARLY MORTALITY IN PATIENTS HOSPITALISED WITH HIV- ASSOCIATED TUBERCULOSIS: CHARACTERISING THE IMMUNE RESPONSE ASSOCIATED WITH DEATH 1C. Schutz, 2D. Barr, 1A. Ward, 3S. Janssen, 4R. Burton, 5R.J. Wilkinson, 5K.A. Wilkinson, 1M. Shey, 1G. Meintjes 1 Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town (UCT), and Department of Medicine, UCT, South Africa; 2 Wellcome Trust Liverpool Glasgow Centre for Global Health Research, University of Liverpool, United Kingdom; 3 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; 4 Khayelitsha Hospital, Department of Medicine, UCT, South Africa; 5 Department of Medicine, Imperial College and The Francis Crick Institute, London, United Kingdom

BACKGROUND RESULTS TB remains the leading cause of death Of the 682 patients who were enrolled, (40%), hospitalisation (18%) and in-hospital 571 were diagnosed with TB. TB was death (25%) in HIV-infected people microbiologically confirmed in 482/571 worldwide. Despite availability of effective (84.4%), 123/571 (21%) died within 12 anti-TB and HIV treatment there is high early weeks despite 560/571 (98%) starting on mortality, especially in hospitalised patients. TB treatment. We identified a principal The pathophysiology underlying death in component (PC1) which accounted for 25% hospitalised HIV-infected patients newly of data variability and was dominated by diagnosed with TB is poorly understood. innate immune signalling and chemotaxis (IL-8, IL-6, IL-1Ra, MIP-1, MCP-1). PC2 OBJECTIVE explained 24% of the variance and was To characterise the immune correlates of dominated by T-lymphocyte-related mortality in patients hospitalised at the mediators (IL-13, IL-7, IL- 12, TNF-, IL-2). time of HIV-TB diagnosis. In Cox proportional hazards, analysis PC1 was associated with mortality (aHR=2.3, METHODS (95%CI=1.9-2.7)) and PC2 with survival We conducted a prospective cohort study (aHR=0.67, (95%CI=0.5-0.9)) after at Khayelitsha Hospital, Cape Town, South adjustment for age, sex and HIV viral load. Africa. HIV-infected patients with CD4 <350 IL-1Ra concentration was six-fold higher in cells/μl and suspected TB were enrolled patients who died within seven days. and those with a diagnosis of TB (n=571) are included in this analysis. Samples CONCLUSIONS were obtained upon presentation, before HIV-infected patients hospitalised at the TB treatment. Twelve-week mortality time of TB diagnosis have high 12-week was ascertained. Twenty-eight soluble mortality. Mortality was associated with markers of inflammation were measured an immune profile of innate immune and in a randomly selected subset of 496 chemotactic signalling, and an immune patients (108 deaths and 388 survivors). profile dominated by T-lymphocyte Statistical analyses were performed in R mediators was protective. (Version3.4.4).

115 TUBERCULOSIS AND THEIR RELATIONSHIP TO INFLAMMATION AT THE SITE OF DISEASE 1,2N.V. Sibiya, 1,2A.K. Coussens, 1,3-5R.J. Wilkinson 1 Clinical Infectious Diseases Research Initiative, University of Cape Town (UCT), Cape Town, South Africa; 2 Department of Clinical Laboratory Sciences, UCT, South Africa; 3 Department of Medicine, UCT, South Africa; 4 The Francis Crick Institute, Mill Hill Laboratory, United Kingdom; 5Imperial College, Department of Medicine, United Kingdom

BACKGROUND CT and to determine whether BAL cells Tuberculosis (TB) remains one of the leading from lung lobes contralateral to the site of causes of death globally, and with the steep subclinical infection have distinct profiles rise in drug resistance (DR), is becoming which may reflect a signature of recent increasingly difficult to manage. Contacts infection in the lung. of DR-TB are at high risk of infection thus, the WHO recommends that this cohort METHODS be screened and treated to minimise the Samples from participants with active TB, chance of developing active TB disease. subclinical TB and no TB will undergo Currently, no methods are available for whole-blood and BAL cellular mRNA diagnosing subclinical TB, where the risk transcriptome analysis. Serum and BAL of progression to active disease is high, but fluid will be characterised and have before people become contagious. Hence, a panel of inflammatory cytokines, there is a need for quick and accurate chemokines, and growth factors measured. subclinical TB diagnostic methods, of Circulation and BAL cell populations will which whole-blood biosignatures is one be immunophenotyped. Systems biology promising candidate. Determination of a approaches in whole-blood and BALF at subclinical TB biosignature can potentially baseline and 6-12 months will be used to be achieved by a combination of methods, identify a biosignature of subclinical TB in such as positron emission tomography- whole blood. computed tomography (PET/CT), to CONCLUSION detect sites of potential lung infection The primary outcome is expected to be a and the characterisation of cellular and validated biosignature for recent infection molecular components of whole-blood and or re-infection that will be developed into a bronchoalveolar lavage (BAL). multiplex assay which could be used as an OBJECTIVES experimental endpoint in vaccine studies. To identify blood biomarkers associated with the presence of subclinical Mycobacterium tuberculosis infection as defined by PET/

116 SAMRC RESEARCH CAPACITY DEVELOPMENT INITIATIVE (RCDI)

MS PHILISTIA JOSHUA – PROGRAMME ADMINISTRATOR

117 117 DETERMINANTS OF TYPE-2 DIABETES MELLITUS AMONG HIV/AIDS PATIENTS ON ANTIRETROVIRAL DRUGS IN THE OR TAMBO DISTRICT, SOUTH AFRICA 1N.E. Bam, 1T. Apalata, 1M. Ntsaba 1 Faculty of Health Sciences, Walter Sisulu University, Mtatha

BACKGROUND relationship (ρ=0.017), physical inactivity Among patients on antiretroviral therapy (ρ=0.013), inadequate diet (ρ=0.031), (ART), the World Health Organization uncontrolled high blood pressure (ρ=0.024), (WHO) suggests that chronic diseases, absence of salt reduction (ρ=0.023), and mainly cardiovascular diseases and type- the use of any ART (ρ <0.0001) were 2 diabetes mellitus (DM) should be independently associated with the presence monitored. of type-2 DM among HIV-infected patients. The mean duration on ART was 5.96 (± OBJECTIVES 3.01) years for cases as compared to 4.61 To describe determinants of type-2 DM (± 2.73) years for controls (ρ <0.0001). As among HIV/AIDS patients on ART in the OR compared to HIV-infected patients who Tambo District and develop intervention received ART for ≤ five years, the risk of strategies able to mitigate the long-term developing type-2 DM was two and three effects of type-2 DM. times higher for patients who received ART between 6−10 years (ρ <0.0001) METHODS and ≥11 years (ρ=0.035), respectively. As A case-control study was conducted on compared to patients who received fixed- a retrospective cohort of HIV-infected dose combination ART, the risk was 22 to patients. Cases were defined as HIV- 43 times higher for developing type-2 DM positive patients with type-2 DM, while if any protease inhibitor was part of the controls were HIV-positive without type- regimen, while this risk ranged from two 2 DM. We used a self-administered and a half to nine times higher if any non- questionnaire adapted from the WHO nucleoside reverse transcriptase inhibitor STEPwise surveillance tool. was part of the regimen (ρ <0.0001). RESULTS Of patients (n=531) enrolled (87.19% CONCLUSION Traditional risk factors compounded by females and 12.81% males), 177 were ART-associated adverse events are the cases and 354 controls. Secondary level principal drivers of type-2 DM among HIV- of education (ρ=0.036), unstable marital infected patients.

118 FACTORS ASSOCIATED WITH RECENT UNSUPPRESSED VIRAL LOAD IN HIV-1-INFECTED PATIENTS RECEIVING FIRST-LINE ANTIRETROVIRAL THERAPY IN AN NHI PILOT DISTRICT IN EASTERN CAPE, SOUTH AFRICA 1T. Apalata, 1N. Pakade, 1M. Ntsaba 1 Faculty of Health Sciences, Walter Sisulu University, Mtatha

BACKGROUND with unsuppressed VL at the most recent In 2016, approximately 834,253 people visit among patients in care. were living with HIV and 360,206 people receiving antiretroviral therapy (ART) in RESULTS the Eastern Cape (EC). Unsuppressed viral The median age of the 55.6% females load (VL) in patients on ART occurs when and 44.4% males who started on ART, treatment fails to suppress a person’s VL on was 46 years and their median duration first-line ART for ≥ six months. of ART was nine years. After adjusting for confounding variables, factors associated OBJECTIVES with unsuppressed VL included: less than To evaluate factors associated with ten years’ duration on ART (OR=1.83; CI: unsuppressed VL (VL > 400 copies/ml) 1.2–2.98; ρ=0.016), WHO disease stage to inform interventions to improve VL 2 (ρ <0.0001) and stage 3 (ρ=0.004), and suppression among patients currently in initial VL ≥ 10,000 copies/mL (ρ=0.047). care. Approximately 62.8% of the ART cohort who were in care had achieved viral METHODS suppression, far below the UNAIDS 90% Routinely collected data from patients’ target. T-test for paired samples showed a medical records and electronic TIER. significant difference between initial CD4+ Net record system were used in a cross- T cells (108.51 ± 55.68 cells/mm3) and sectional analysis of a cohort of HIV most recent CD4+ T cells (781.72 ± 219.95 patients in care. Seven primary health-care cells/mm3) (ρ <0.0001). facilities in OR Tambo, a selected NHI pilot district in the EC, were targeted. A total CONCLUSION of 360 patients on first-line ART for ≥ six There is a need to develop and evaluate months were included. A multivariate targeted interventions for ART patients in logistic regression analysis was used to care who are at high risk of unsuppressed identify factors independently associated VL.

119 TASK-SHIFTING FOR ANTIRETROVIRAL TREATMENT DELIVERY AND QUALITY OF HIV/AIDS CARE INITIATED BY NURSES AT PRIMARY HEALTH-CARE LEVEL IN EASTERN CAPE, SOUTH AFRICA 1T. Apalata, 1N. Pakade, 1M. Ntsaba 1 Faculty of Health Sciences, Walter Sisulu University, Mtatha

BACKGROUND did not readily accept task-shifting and Since 2011, task-shifting has been objected to delegate their tasks; they advocated as a strategy for addressing the perceived that patients would probably health-care worker shortages impeding change facilities to avoid nurses. There was scaling up of ART programmes in South an increased loss to follow-up rate of HIV Africa. Limited evidence on the success of patients in some clinics. Patients (67.2%) this programme in Eastern Cape province were more likely to report dissatisfaction exists. with services received from nurses, which was not significantly associated with the OBJECTIVES presence of unsuppressed viral load. To assess the acceptability of HIV Absence of regular transport by 40% of management by nurses and evaluate patients and long waiting time in clinics effects of perceived quality care delivery were more likely to be associated with and satisfaction on patients’ outcomes. lower CD4 counts after ≥ six months of ART (ρ <0.0001). Only 20% of nurses perceived METHODS their own knowledge and skills about HIV A cross-sectional study was conducted in management as adequate and satisfactory, seven randomly selected primary health- while 43.3% and 16.7% reported not care facilities in OR Tambo district. Data being trusted by patients and doctors, were collected from seven doctors, 30 respectively. Challenges included lack of nurses, seven managers and 360 patients policies, absence of standardised training, using structured interviews. Responses various degrees of supervision, mentorship from open-ended questions were coded and nurses’ performance evaluation. to generate quantifiable responses and analysed using SPSS v24. CONCLUSION Patients’ dissatisfaction with task-shifting RESULTS might explain the high rate of loss to Managers, doctors and nurses believed follow up in some clinics. Addressing the task-shifting would improve access to identified challenges is urgently warranted and quality of HIV services. Some doctors for improving quality care.

120 THE PROPOSED ADAPTATION AND IMPLEMENTATION OF ACUTE CARE CLINICAL GUIDELINES IN THE MANAGEMENT OF TRAUMATIC SPINAL CORD INJURIES FOR THE SOUTH AFRICAN CONTEXT: A DELPHI CONSENSUS STUDY PROTOCOL 1B Boggenpoel, 1N. Mlenzana, 1A. Rhoda, 1,2C. Jospeh 1 The University of the Western Cape, Department of Physiotherapy, Bellville, Cape Town, South Africa; 2 Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Physiotherapy Division, Stockholm, Sweden

BACKGROUND using thematic analysis, while the mean will The use of acute care clinical guidelines be used to document the level of consensus for traumatic spinal cord injury (tSCI) in round two and three. All participants will management proves to be invaluable in be given an information sheet detailing improving the processes of care being the purpose of the study and requested to delivered within the hospital setting. give written informed consent online. To However, areas in need of change and facilitate the dissemination of findings, a strengthening, as well as barriers to the presentation will be given to relevant end- implementation of these guidelines within users/stakeholders. Ethics will be sought the South African context, still need to be from the University of the Western Cape answered. Research Ethics Committee, specifically the Humanities and Social Sciences Research OBJECTIVE Ethics Committee. To develop recommendations for improving the use of acute care guidelines in tSCI RESULTS management by taking into account the The results will be dependent upon the health structure, function, resources and outcomes of the Delphi study. constraints specific to our setting. CONCLUSIONS METHODS Identifying the areas within which acute A three-round Delphi method will be used care guidelines can be changed to suit our to explore and reach consensus as to which local context would be key in facilitating its areas of the international guidelines should uptake, and successful implementation. The be changed, as well as highlight their findings of this study, will further provide us possible barriers to implementation. For with a starting point as to the areas that the purposes of this study, the agreement may need adaptation or contextualisation level for consensus will be set at 70%. to improve patient outcomes and current Qualitative data, as collected through processes of care. open-ended questions, will be analysed

121 INTEGRATIVE ANALYSIS OF EPIGENETIC MODIFICATIONS IN A BREAST CANCER CELL LINE TREATED WITH A BIOACTIVE EXTRACT OF BIDENS PILOSA 1P.K.P. Chokoe, 2C. Pheiffer, 1L.J. Mampuru 1 Department of Biochemistry, Microbiology and Biotechnology, Faculty of Science and Agriculture, University of Limpopo, Sovenga, South Africa; 2 Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa

BACKGROUND hexane, chloroform, ethyl acetate, butanol, The global incidence of breast cancer methanol and water. The chloroform has continued to increase over the years. fraction showed the most sought-after Conventional therapies, such as radiation activity, lowering the viability of MCF-7 and surgery, for the malignancy, are often breast cancer cells by more than 40% at undesirable. Moreover, therapy involving concentrations above and including 200 drugs often results in side effects affecting µg/ml after 24 hours. The effect of the B. the health of the patient. Phytochemicals pilosa chloroform fraction on alterations in have proven to offer effective alternatives the epigenetic mechanisms underpinning to conventional medication for treatment breast cancer will be investigated in this of many ailments and clarification of study. This will be achieved primarily by their mode of action is essential for their assessing telomerase activity, global DNA development as potential treatments for methylation and the methylation status cancer. of breast cancer-associated genes using bisulfite pyrosequencing as well as a OBJECTIVE histone modification assay in treated MCF- To investigate the potential of Bidens 7 cells. Furthermore, expression of genes pilosa to mitigate cancer progression by shown to be differentially methylated in modulating epigenetic mechanisms in the breast cancer cells will be quantified using MCF-7 breast cancer cell line. quantitative RT-PCR and Western blot analysis in MCF-7 cells treated with the METHODS crude B. pilosa extract and its chloroform The crude methanolic extract of B. pilosa fraction. was separated into six fractions of varying polarity which were then assayed for their RESULTS AND CONCLUSION cytotoxicity using the MTT assay. The Not yet available. solvents used in the fractionation were

122 DEVELOPING A MODEL FOR PROMOTING PHYSICAL FITNESS AND HEALTHY LIFESTYLE OF PRIMARY SCHOOL LEARNERS IN THE EASTERN CAPE PROVINCE, SOUTH AFRICA 1H. Gomwe, 1E. Seekoe, 1P. Lyoka 1 Faculty of Health Sciences, University of Fort Hare, East London

BACKGROUND sample of 876 learners aged 9–14 years. Data The challenge of low-level participation collection includes demographic, lifestyle in physical activity (PA) and, consequently, behavioural variables, anthropometric, limited physical fitness has been physical fitness measurements and six acknowledged as being a national public focus group discussions. health concern in South African schools. The first thing was to determine their physical RESULTS fitness level and body composition and then Out of 876 participants, 61.76%, 3.77%, develop a behavioural model based on the and 2.16% were underweight, overweight findings. In the Eastern Cape, there isno and obese, respectively. Boys reported such model for promoting physical fitness higher PA levels than girls (p<.0001). PA among the children. The model by policy levels decreased with age from 9–14 years makers, institutions, and the community and there were also significant differences will stem the tide of low physical fitness and in PA levels between gender and residences the rising trend of overweight and obesity (p<.000). Body composition measures were among these children. reported higher in girls than boys, and higher in urban areas compared to rural OBJECTIVE areas. To develop a behavioural model for promoting physical fitness and healthy CONCLUSIONS lifestyle of primary school learners in the In this study, we demonstrated the Eastern Cape Province in South Africa. prevalence of overweight, obesity, underweight, and low level of physical METHODS fitness among the school learners. These The researcher employed a cross-sectional, findings form the basis for developing mixed-method, descriptive and theory a model for promoting physical fitness generating research design to develop and healthy lifestyle in the South African the model for promoting physical fitness context. and healthy lifestyle of the primary school children. The study involved a random

123 TRAINING NEEDS FOR THE IMPLEMENTATION OF THE 2012 INTEGRATED SCHOOL HEALTH POLICY IN THE EASTERN CAPE PROVINCE 1D.T. Goon, 1U. Obi, 1E. Seekoe 1 Faculty of Health Sciences, University of Fort Hare, East London Campus, Eastern Cape

BACKGROUND attended workshops to integrate and International evidence shows that the understand the HIV policy; first aid; school implementation of successful school nutritional policies; financial issues; and fire health programmes depends on strong extinguishers. Most school principals were partnerships between education and not trained in ISHP. The LO teachers and health sectors, teachers and health Director of Social Development did not workers, schools and community groups, receive any form of training in ISHP. The and learners and persons responsible for LO teachers expressed the desire to be school health programmes. trained in counselling; health and physical education; HIV/AIDS; and drug abuse. The OBJECTIVE school principals indicated the need to To assess the training needs of various provide a mentorship programme where stakeholders responsible for implementing some principals shall be mentored by other the Integrated School Health Policy (ISHP) principals. They also emphasised training in the Eastern Cape. on aspects of HIV/AIDS and nutrition education. Because of the shortage of staff, METHODS staff nurses are not able to attend in-service Individual face-to-face interviews were training. They had training in school health; conducted with primary and secondary Human Papillomavirus but could not be school principals, Life Orientation (LO) trained on Ward Based Outreach. teachers, and the Directors of Education, Health and Social Development to CONCLUSIONS assess their training needs for effective The principals, teachers, and Directors implementation of the ISHP. signified their ambition to be trained in the implementation of ISHP. Their RESULTS training needs were identified, and The participants indicated that training recommendations made to ensure the for the implementation of the ISHP was ISHP implementation is more effective in not satisfactory. However, there is training schools for the optimal development of all on capacity building regarding the school children. implementation of ISHP and supported by the coordinator of HIV. The teachers

124 DESIGN, SYNTHESIS AND IN VITRO BIO-ANALYTICAL TESTS OF NEW CHEMICAL ENTITIES AS CYP17A1 INHIBITORS: TARGETING PROSTATE CANCER 1N. Gumede 1 Department of Chemistry, Mangosuthu University of Technology, Umlazi, Durban

BACKGROUND testing using ultra-high-performance liquid Metastatic castration-resistant prostate chromatography (UHPLC-MS/MS). cancer (mCRPC) is a major problem mostly in older males. Since current medications RESULTS are rendered ineffective by mutations and The compounds in the dataset that splice variants of the androgen receptor, remained (after outlier-elimination) survival rates are very low. provided adequate model predictive statistics (R2=0.9228 and Q2=0.9400, OBJECTIVES for training and test sets, respectively). To design CYP17A1 inhibitors targeting Density functional theory optimisation the lyase route of the enzyme, instead of further provided the electronic properties the hydroxylase route that is susceptible to explaining their structure activity mineralocorticoid excess syndrome. Hence, relationships (SAR). Finally, docking abiraterone acetate is co-administered with revealed the binding modes of new prednisone. chemical entities (NCEs) at molecular level explaining their experimental binding METHODS affinities to CYP17A1 enzyme. We performed a 3D-QSAR pharmacophore model on a diverse set of steroidal CONCLUSIONS and non-steroidal CYP17A1 inhibitors The 13 hits designed computationally obtained in the literature. Using the highly were synthesised in the laboratory as active, medium and inactive compounds different scaffolds. The UHPLC-MS/MS in the dataset, we selected a six-point in vitro experiments revealed three NCEs pharmacophore hypothesis with the unique with IC50 values against the lyase route at geometrical arrangement of two hydrogen sub-micromolar level, on the synthesised bond acceptors (A), one hydrogen bond molecules. Conversely, the hydroxylase donor (D), one hydrophobic group (H), and route gave IC50 values >50 µM. The two aromatic rings (R). Database screening three most promising inhibitors identified and molecular docking of the hits followed, could be further optimised to improve which were subsequently synthesised their potency against CYP17A1, the target in the laboratory before bio-analytical enzyme.

125 STAT-1 IS REQUIRED FOR THE INDUCTION OF INTERFERON INDEPENDENT CHOLESTEROL 25-HYDROXYLASE 1T. Magoro, 1P.O. Bessong, 2A.P. Dandekar, 2Y.S. Hahn, 2L.T. Jennelle, 2R. Rabab 1 Department of Microbiology, University of Venda, Thohoyandou, South Africa; 2 Department of Microbiology, Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, USA

BACKGROUND RESULTS Although cholesterol 25-hydroxylase In this study, we showed that CH25H is (CH25H) and its metabolite, induced by ZIKV infection, TLR stimulation, 25-hydroxycholesterol (25HC) have been and 25HC efficiently inhibited ZIKV shown to exert broad antiviral properties, infection at a post-entry stage. Interestingly, suppressing viral pathogen. However, CH25H was induced by pro-inflammatory in humans, its transcriptional regulatory cytokines including IL-6, 1L-1b, and TNF-a events are critical to understanding to and this induction was dependent on STAT- further design therapeutic agents to control 1 transcription factor. Additionally, we viral infection. have observed that ATF3 weakly binds to CH25H promoter suggesting co-operative OBJECTIVE operation with STAT-1. However, ZIKV To understand the regulation of CH25H to induced CH25H was independent of this further design therapeutic agents to control pro-inflammatory cytokines or interferons, viral infection. which further complicates CH25H transcriptional regulatory events in humans. METHODS Wildtype THP-1 monocytic cell-line CONCLUSIONS or THP-1 MyD88 knockout cell-line Our results have demonstrated for the were treated with PMA for 72 hours for first time the ability of pro-inflammatory differentiation into macrophages. For cytokines to induce CH25H. These findings resident macrophages, human microglial will guide us to understand the regulation cells were utilised. Macrophages were then of CH25H in human cells better. Our data stimulated with either TLR-agonists, pro- also contribute to a rapidly growing body inflammatory cytokines, ZIKV or interferons, of evidence that identifies 25HC as a and several interferons stimulated genes potent antiviral agent. including CH25H, mRNAs expression levels were measured by qPCR.

126 INVESTIGATION OF THE PROBABLE ANTI-CANCER EFFECTS OF THE CRUDE METHANOL EXTRACT OF DICEROCARYUM SENECIOIDES, (KLOTZCH) J. ABELS, LEAVES ON CERVICAL HELA CANCER CELLS 1K. Malemela, 2S. Riedel-van Heerden, 1V. Mbazima 1 Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Sovenga, South Africa; 2 Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, Tygerberg, South Africa

BACKGROUND mechanisms of the extract. Cervical cancer accounts for 7.6% of all cancer deaths worldwide. In South Africa, it RESULTS is among the five most prevalent cancers in The extract showed significantly increased women. Although substantial progress has inhibition of HeLa cell viability at been made in current treatments, they have concentrations above 400 µg/ml after 48 shown limited survival benefits for most hours. Extract concentrations below 600 advanced-stage cancers. Dicerocaryum µg/ml showed no effect on the viability senecioides is a plant widely used as a of normal human fibroblast KMST-6 cells. nutritional source and treatment of measles Apoptosis was proposed as the mode of and wounds in many parts of southern cell death in extract-treated HeLa cells. Africa. There was modulation of some anti- and pro-apoptotic proteins as well as the release OBJECTIVE of mitochondrial proteins required for the To investigate the anti-cancer effects of initiation of apoptosis in the cytoplasm. the crude methanol leaf extract of D. senecioides on HeLa cells. CONCLUSION Dicerocaryum senecioides crude methanol METHODOLOGY leaf extract induced some degree of Cytotoxicity was assessed using the MTT apoptosis in cervical HeLa cancer cells via assay and the mode of cell death by the the intrinsic apoptosis pathway. Hoechst 33258 nuclear staining assay and inverted light microscopy. Flow cytometry was used to confirm the mode of cell death using the annexin-V/PI and multicaspase assays. Western blotting analysis and the human apoptosis antibody array kit were used to elucidate pro-apoptotic

127 GENETIC VARIATION WITHIN THE CODING REGION OF CCR5 IN CHRONICALLY HIV-1 INFECTED SOUTH AFRICAN INDIVIDUALS 1N.D. Matume, 2D.M. Tebit, 2 L.R Gray, 2D. Rekosh, 2M-L. Hammarskjöld, 1P.O. Bessong 1 HIV/AIDS & Global Health Research Programme, Department of Microbiology, University of Venda, Thohoyandou, South Africa; 2 Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, USA

BACKGROUND reported in the 1000 Genome Phase III The human co-receptor CCR5 is an and HapMap. Hardy-Weinberg Equilibrium important target for viral and cellular was calculated, Haplotypes and Linkage antiretroviral interventions. Until now, disequilibrium were inferred using LDlink several mutations and single-nucleotide 3.0 web tool. polymorphisms (SNPs) in this gene have been discovered and found to be important RESULTS genetic factors capable of influencing We detected the following SNPs P35P, susceptibility to HIV-1 infection or affecting S75S, Y89Y, A335V and Y339F and their the rate of disease progression. varying frequencies in this study. The A335V and Y339F variants were detected at the OBJECTIVE highest frequency of 17.4% (29/167) and To characterise polymorphism in the coding 1.2% (2/167), respectively than previously region of CCR5 in an HIV-1 infected South reported in South Africa. The G265S African population of which most were variant is reported for the first time at 0.6% drug-experienced. (1/167) frequency. The SNPs detected were in strong LD (D’=1, R2=0.0) with a METHODS minor deviation from the Hardy-Weinberg Genomic DNA was isolated from Equilibrium. peripheral blood mononuclear cells of 192 HIV-infected patients and CCR5 CONCLUSIONS was sequenced on an Illumina MiniSeq We have shown that significant SNP platform. Sequences were analysed using variation and frequency distribution exist Geneious® software version 8.1.5. SNPs among diverse populations in South Africa and Indels were detected using Bayesian and that the variants detected in the study Haplotype-based polymorphism discovery cohort are not located in the binding motif and genotyping tools within Geneious of Maraviroc. Therefore, those infected with software. The SNPs were confirmed and CCR5 utilising viruses may benefit from the compared to SNPs in other populations use of this in HIV treatment.

128 PREVALENCE OF OBESITY, HYPERTENSION AND ERECTILE DYSFUNCTION AMONG HIV –VE AND NEWLY DIAGNOSED HIV +VE ART NAÏVE PATIENTS 1V. Mbombela, 1C. Sewani-Rusike, 1H. Musarurwa, 2B. Nkeh-Chungag 1 Department of Human Biology (Physiology), Walter Sisulu University, Mthatha; 2 Department of Zoology, Walter Sisulu University, Mthatha

BACKGROUND systolic and diastolic BPs were recorded. A Classic risk factors for cardiovascular validated structured questionnaire (IIEF15) diseases (CVD) such as age, obesity and was used to assess erectile dysfunction. hypertension, have been increasingly Data are reported as mean ± SEM and reported among patients on antiretroviral frequency %. therapy, yet data on the prevalence of these parameters among newly diagnosed RESULTS male patients compared to HIV-negative The mean age of the HIV +ve group was population is scarce. Erectile dysfunction higher (P<0.001) compared to the HIV – is considered an early indicator of CVD ve group (34.0 ± 0.9 years vs 29.63 ± 0.8 although underreported. years). Despite the younger age, HIV -ve group had a higher (P<0.05) prevalence of OBJECTIVE abdominal obesity (W:H ≥0.9; 27% vs 15%) To investigate the prevalence of and overweight + obesity (BMI ≥25; 26% hypertension, obesity and erectile vs 16.6%) compared to HIV +ve but similar dysfunction among newly diagnosed ART prevalence of hypertension (BP ≥140/90; naïve HIV-infected men (HIV +ve) compared 31% in HIV –ve vs vs 26% in HIV +ve). to HIV-negative (HIV –ve) participants. The overall prevalence rate for erectile dysfunction was 50% for HIV –ve and 58% METHODS for HIV +ve (P>0.05). One hundred and three HIV –ve and 66 HIV +ve participants were recruited from CONCLUSIONS a primary health-care testing centre in These preliminary data show a high Mthatha. After giving informed consent, prevalence of hypertension and erectile anthropometric measurements for dysfunction in a young population of HIV the calculation of waist:hip ratio (W:H, –ve and HIV +ve men. Anthropometric risk abdominal obesity) and body mass index factors for CVD are more prevalent in HIV (BMI) were taken. Blood pressure (BP) was –ve than HIV +ve men. measured in triplicate, and the means of

129 IN VITRO ASSESSMENT OF CYTOCHROME P450 AND DRUG TRANSPORTERS MODULATION BY POLYPHENOLIC CONSTITUENTS OF CYCLOPIA GENISTOIDES 1,2N. Mchunu, 2S. Bowles, 2C. Muller, 1P. Kappo, 3C. Malherbe, 2C. Awortwe 1 Department of Biochemistry and Microbiology, University of Zululand, Kwadlangezwa, South Africa (SA); 2 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, SA; 3 Post-Harvest and Wine Technology Division, Agricultural Research Council, Infruitec-Nietvoorbij, Stellenbosch, SA

BACKGROUND RESULTS Herb-drug interactions (HDI) are C. genistoides was deemed non-toxic to acknowledged as a growing public health C3A hepatocytes, and showed inhibitory problem that can lead to life-threatening activities on all CYP isoforms tested (53%, adverse drug reactions (ADR). The potential 54.74%, 68.83% and 76.56% inhibition of for ADR requires assessment before CYP3A4, CYP2D6, CYP2C19 and CYP2C9, herbal products are made available on respectively). Mangiferin inhibited CYP the market. In this study, we assessed the 3A4 (60.83 % inhibition), CYP2D6 (52.12% effect of a Cyclopia genistoides extract for inhibition) and CYP2C9 (82.08% inhibition). its interaction with cytochrome P450 (CYP) The xanthone-rich fraction inhibited enzymes and drug transporters. CYP3A4 (52.5% inhibition) and CYP2D6 (50% inhibition) while the benzophenone- OBJECTIVE rich fraction only showed inhibition of To investigate whether the use of C. CYP3A4. RT-PCR analysis suggested that genistoides extract or its bioactive phenolic the extract, xanthone-rich fraction and constituents has the potential for herb-drug mangiferin as a pure compound, affect the interactions. expression of major drug transporters.

METHODS CONCLUSIONS The potential for hepatotoxicity of a methanol Xanthone-enriched extracts, especially C. genistoides extract, xanthone and those with a high mangiferin content, show benzophenone enriched fractionations and potential towards herb-drug interactions associated pure compounds (mangiferin, and warrant further investigation into the isomangiferin, 3-β-D-glucopyranosyl-4-β- potential of ADR. qRT-PCR analysis to show D-glucopyranosyloxyiriflophenone (IDG) how these extracts affect the expression and 3-β-D-glucopyranosyliriflophenone of major drug transporters needs to be (IMG)) was assessed using C3A liver cells. performed. The inhibitory effects of these compounds on major CYP isoforms were also assessed using Vivid® blue screening kits.

130 AN INTERSECTORAL COLLABORATION MODEL FOR THE IMPLEMENTATION OF THE INTEGRATED SCHOOL HEALTH POLICY IN THE EASTERN CAPE PROVINCE, SOUTH AFRICA 1S. Mnwana, 1E. Seekoe, 1D. Goon 1 Department of Nursing, Faculty of Health Sciences, University of Fort Hare, East London, Eastern Cape

BACKGROUND METHODS The need for intersectoral collaboration in This study will adopt a qualitative, the provision of school health services is explorative, and descriptive and theory well recognised internationally as a cost- generation research design. A purposive effective strategy and thus reaching groups sampling technique will be used to select with great need and limited resources. The the participants. Face-to-face semi- collaboration model provides a conceptual structured interviews will be utilised for data framework on which to base action and a collection. Data will be analysed guided by standard against which to measure success grounded theory. and simplifies the complex process of providing school health programmes. CONCLUSIONS The findings and recommendations of OBJECTIVES this study might help to strengthen the The research objectives for this study are intersectoral collaboration among the key to, 1.) examine the nature of collaboration stakeholders involved in the implementation that exists between the stakeholders of the ISHP in the Eastern Cape, and by implementing the integrated school health extension, South Africa. Recommendations policy (ISHP); 2.) describe the barriers and from this study may be useful to policy facilitators of collaboration; 3.) describe makers at national and provincial levels in the collaborative needs of the stakeholders designing and implementing school health- in implementing the ISHP; 4.) describe a related policies and interventions in South conceptual framework that can be used Africa, taking into perspective the need for to develop the intersectoral collaboration intersectoral collaborative paradigms. model; and 5.) develop a model to facilitate collaboration between the stakeholders.

131 PHYTOCHEMICAL ANALYSIS OF ETHYL ACETATE AND METHANOL EXTRACTS OF SENNA ITALICA 1M. Moloantoa, 1M. Mokgotho, 1K. Poopedi, 1L. Mampuru 1 Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Sovenga

BACKGROUND using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) The bioactive phytochemicals present in radical scavenging activity assay. plants are preferred for anti-cancer therapy because of their potential to differentiate RESULTS between cancerous and normal cells. The Phytochemicals such as the phenols, plant species, Senna italica, is indigenous tannins, flavonoids, terpenoids and in Southeast Asia and Sub-Saharan Africa. steroids were abundant in the ethyl As a herbal/traditional medicine, the acetate extract compared to the methanol stems are used to treat diabetes, malaria, extract. Additionally, the ethyl acetate constipation, jaundice and fever. extract exhibited more antioxidants and indicated more radical scavenging activity OBJECTIVE in comparison to the methanol extract. To determine the antioxidant and phytochemical properties of Senna italica CONCLUSIONS leaf extract using the ethyl acetate and The phytochemical and antioxidant methanol solvent systems. properties of S. italica were dependent on the solvent system that was used in METHODOLOGY the extraction process. In this study, the Senna italica leaves were extracted with ethyl acetate solvent system was more ethyl acetate and methanol. Phytochemical prominent in extracting phytoconstituents analysis was determined using thin layer which contributed to the antioxidative chromatography. Various phytoconstituents property of the extract. were evaluated using standard chemical tests. Antioxidant activity was determined

132 MOMORDICA BALSAMINA INDUCES P53-MEDIATED APOPTOSIS ASSOCIATED WITH G0/G1 CELL DIVISION CYCLE ARREST IN LUNG A549 CANCER CELLS 1M. Mudalahothe, 1K. Lebogo, 1K. Malemela, 1V. Bagla, 1M. Mokgotho, 1L. Mampuru, 1V. Mbazima 1 Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Sovenga, Limpopo Province, South Africa

BACKGROUND associated with apoptosis was analysed Apoptosis is a process of programmed by AO/EB and annexin V-7-ADD staining. cell death with unique morphological Furthermore, the effect of the extract on the and biochemical changes, such as cell cycle arrest and associated genes and cell shrinkage, nuclear fragmentation, apoptosis regulatory genes was measured chromatin condensation and using the Muse cell cycle assay kit and RT- externalisation of phosphatidylserine. The PCR technique, respectively. process of eliminating the damaged cells susceptible to develop cancer further aids RESULTS apoptosis as a defence mechanism for The extract inhibited the viability and cancer development. Hence, screening of proliferation of A549 cells in a time- and medicinal plants for anti-cancer activity, in concentration-dependent manner following vitro, could help identify plant extracts with 24 and 48 hours of treatment. Chromatin the potential to induce apoptosis without condensation, nuclear fragmentation affecting normal cells. and externalisation of phosphatidylserine were observed, suggesting the induction OBJECTIVE of apoptosis. The extract was also seen To investigate the ability of Momordica to induce G0/G1 and G2/M phase arrest balsamina’s crude leaf acetone extract to and modulate cell cycle and apoptosis induce apoptosis in lung A549 cancer cells. regulatory genes.

METHODS CONCLUSION The effect of the extract on cell viability Momordica balsamina has an anti- and proliferation was determined using proliferative effect and induces apoptosis Muse viability and Ki67 proliferation assay cell death associated with cell cycle arrest kits, respectively. The presence of features at G0/G1 and G2/M phase.

133 GENETIC DIVERSITY OF SLCO1B1 WITHIN INDIGENOUS SOUTH AFRICANS AND IMPACT ON ENALAPRIL THERAPY 1R. Musoliwa, 2R. Johnson, 1M. Benjeddou 1 Precision Medicine Unit, Faculty of Natural Sciences, University of the Western Cape; 2 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg

BACKGROUND therapy. The study sample comprised Hypertension is one of the most common patients who were grouped into (i) conditions and was recorded as the number those who were controlled, and (ii) one killer worldwide. More than 60% of those who were uncontrolled. SLCO1B1 hypertensive patients do not respond to promoter and four common exon single antihypertensive drugs. Moreover, some nucleotide polymorphisms (SNPs; have been reported to experience adverse rs4149056, rs2306283 rs11045819 and drug reactions. Enalapril is an angiotensin- rs34671512) were amplified, sequenced, converting enzyme inhibitor, known to and their impact predicted using various exert many beneficial effects that reduce bioinformatics tools. mortality and morbidity in patients with hypertension. Enalapril is important since RESULTS it stabilises blood pressure. However, if One promoter SNP was identified, and it accumulates in the body, patients may three haplotypes generated in the study experience inflammation, body pain, fever cohort. In-silico analysis showed that each and cough. Previous studies have linked haplotype might affect the binding of the genetic variants in the SLCO1B1 gene transcriptional factors. to affect the pharmacokinetics of this drug CONCLUSIONS leading to adverse reactions. The identified haplotypes for the promoter OBJECTIVE of SLCO1B1 may influence the rate of To investigate the genetic variation of protein expression. Further investigation SLCO1B1 in a South African indigenous into the effect(s) that promoter haplotypes population and its role in enalapril response. may have on the response of enalapril needs to be investigated. METHODS DNA was extracted from hypertensive patients who were undergoing enalapril

134 CHALLENGES FACED BY SCHOOL HEALTH NURSES IN THE IMPLEMENTATION OF THE 2012 INTEGRATED SCHOOL HEALTH POLICY IN THE EASTERN CAPE PROVINCE, SOUTH AFRICA 1E. Seekoe, 1D.T. Goon, 1B. Mayeye, 1U.N. Obi 1 Faculty of Health Sciences, University of Fort Hare, East London Campus, Eastern Cape

BACKGROUND RESULTS Children’s need should be made a priority The findings indicated a shortage of in the country. However, meeting this school health nurses, unavailability of obligation has been a challenge due to the equipment, shortage of transport and following reasons: poverty related illnesses long travelling distances, ineffective namely: childhood infectious diseases and Ward-Based Outreach Team initiatives, malnutrition, which in turn become barriers and a lack of stationery for recording and to optimal health and development. The writing referrals. Others include inadequate anecdotal evidence portrays the ineffective training of enrolled nurses in school implementation of the Integrated School health-promotion activities; inadequate Health Policy (ISHP) in the Eastern Cape implementation and management of Province. the school health programme; lack of formalised collaboration and coordination OBJECTIVE with the Department of Education and To improve learners᾿ health by linking Social Development. school visits with the inter-sectoral collaboration required for promoting the CONCLUSIONS health of learners. The sub-optimal provision of school health services in this setting is linked to the METHODS shortage of school health nurses, lack of Face-to-face interviews involving five equipment, transport and long travelling school health nurses and two coordinators distances. For nurses to efficiently perform of the Mother, Child and Women’s᾽ Health their function in the ISHP, human and programme in three Eastern Cape Province material/physical resources are needed. districts were conducted regarding challenges in implementing the (ISHP) programmes. Transcripts were coded thematically.

135 EVALUATING THE SCHOOL FOOD AND NUTRITION ENVIRONMENT IN THE EASTERN CAPE SOUTH AFRICA: IMPLICATION FOR HEALTHY EATING OF SECONDARY SCHOOL LEARNERS 1A.P. Okeyo, 1E. Seekoe, 2A. de Villiers, 2M. Faber 1 Faculty of Health Sciences, University of Fort Hare; 2 Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg

BACKGROUND and pop-corn. Learners’ lunch-boxes Learners in Eastern Cape secondary schools contained samp, noodles, fat-cake, chips, tend to be obese, which is speculative and Russian/Viennas. Few schools had according to the literature. To promote vegetable gardens. Most learners (72.7%) healthy eating practices in learners, the ate breakfast, while more male (24.4%) secondary school food and nutrition than female (29.1%) learners skipped environment needs to be improved. breakfast. Most (62.2%) learners had poor nutritional knowledge; with more male OBJECTIVE (35%) than female (27%) learners having To assess school food and nutrition poor nutritional knowledge. Only 28.6% of environment, eating practices and nutrition LO teachers had received nutrition training, knowledge of secondary school learners in mostly at the Department of Education the Eastern Cape, South Africa. workshops. Despite the poor level of training in nutrition, almost all LO teachers METHODS (92.9%) who were interviewed expressed This cross-sectional study involved 18 interest in nutrition. The Integrated School randomly selected secondary schools Health Policy had no on-site services for in three districts of the Province. The nutritional assessment. study sample comprised 1357 randomly selected secondary school learners and a CONCLUSIONS purposive sample of school principals, Life The school food and nutrition environment Orientation (LO) teachers and school health is saturated with food items containing nurses, who completed questionnaires on mostly carbohydrate, and vegetable and nutrition-related questions. fruits were not served regularly. Most learners ate breakfast before coming to RESULTS school. Nutrition knowledge scores in this Five main food items provided by the population were slightly higher among National School Nutrition Programme at urban learners compared to their rural schools included beans, pap, sour-milk, counterparts. However, it was not reflected rice, and samp. Tuckshops sold chips, in their nutritional consumption of healthier sandwich, pap, biscuits, and cake, while foods. vendors sold chips, sandwich, pap, cake,

136 THE ANALYSIS OF THE PHYTOCHEMICAL PROFILE AND ANTIOXIDANT ACTIVITY OF CRUDE METHANOLIC AND SUB-FRACTIONS OF BIDENS PILOSA L 1M. Raboshakga, 1K. Poopedi, 1V. Bagla, 1M. Mokgotho, 1L. Mampuru 1 Department of Biochemistry, Microbiology & Biotechnology, University of Limpopo, Sovenga

BACKGROUND Phytochemical fingerprint profiles of the Plants are an essential remedial source for extracts were established using thin layer prevention, management and treatment of chromatography. Various phytochemical- various ailments in the traditional systems constituents and antioxidant activity were and western medicine. A large percentage determined qualitatively and quantitatively of drugs are derived from natural sources. using standard procedures. The plant Bidens pilosa L (B. pilosa) has been used by the indigenous traditional RESULTS practitioners for treatment of various The crude methanolic extract, 35% water ailments, such as infections, wounds and in methanol and n-butanol extracts burns, inflammation, allergies and malaria. have shown the presence of phenols, The plant has a broad phytochemical tannins, terpenes, steroids, flavonoids composition, is easily accessible and and glycosides. The chloroform sub- assumed safe to use making it a reliable fractions have the highest concentration potential remedial source. of flavonoids while the n-butanol sub- fraction has the most quantity of phenols. OBJECTIVE The chloroform and 35% water in methanol To analyse the phytochemical fingerprint extracts reflected the most prominent and antioxidant properties of crude antioxidant properties qualitatively and methanolic extract and sub-fractions of B. quantitatively. pilosa L. CONCLUSION METHODOLOGY Our findings provided evidence that A crude extract of B. pilosa L was obtained extracts of B. pilosa L contain important by extracting it with methanol. Hexane, medicinally bioactive compounds justifying n-butanol, ethyl acetate, water, chloroform their use in traditional medicine for the and 35% water in methanol sub-fractions treatment of various diseases. were partitioned from the crude extract.

137 THE CONCEPTUALIZATION OF THE 2012 INTEGRATED SCHOOL HEALTH POLICY: IN THE LENS OF PRINCIPALS, LIFE ORIENTATION TEACHERS, SCHOOL GOVERNING BODIES AND WARD COUNSELLORS IN THE EASTERN CAPE, SOUTH AFRICA 1E. Seekoe, 1D. Goon, 1D. Murray, 1N. Mange 1 Faculty of Health Sciences, University of Fort Hare, East London Campus, Eastern Cape

BACKGROUND learners through a range of programmes; The Integrated School Health Policy and curriculum support. From the (ISHP) was implemented at national level findings, it emerged that some of the key to contribute to the improvement of the stakeholders had a clear understanding general health of school-going children. of what the integrated school health The need for the evaluation of the 2012 programme entails. They understood ISHP remains an essential element for that ISHP is a promotive and preventive decision making in social and health policy health-care programme for learners in development. collaboration with the Departments of Health, Education and Social Development OBJECTIVE as well as all relevant structures such as The focus of this study was to assess safety committees and school governing the views of stakeholders regarding the bodies. Participants indicated that the conceptual implementation of the ISHP in integrated school health programme the Eastern Cape, South Africa. provides different health-care programmes such as screening of all the learners, oral METHODS health, eyes, immunisations, mental health, Individual in-depth face-to-face interviews TB, and deworming. The programme also were conducted among the primary and caters for health-care needs and health secondary school principals, including Life problems of learners and the promotion of Orientation teachers, school governing a learner’s lifestyle. bodies and ward counsellors in the OR Tambo; Chris Hani, and Buffalo City CONCLUSION Metropolitan districts in the Eastern Cape Although the concept of ISHP is clearly Province. Interviews were audiotaped and understood by the stakeholders, its thematically analysed. implementation is fraught with several policy and institutional problems for RESULTS effective realisation of its goal of achieving The emerging themes were coordinated optimal health of school children. health-care support in collaboration with relevant stakeholders; enhancing health of

138 THE ANTIMETASTATIC EFFECTS OF MOMORDICA BALSAMINA ON HT- 29 COLON CANCER CELLS 1K. Serala, 1L. Mampuru, 2S. Prince, 1V. Mbazima 1 University of Limpopo Department of Biochemistry, Microbiology and Biotechnology, Sovenga, 2 University of Cape Town, Department of Cell Biology, Observatory

BACKGROUND METHODS Cancer metastasis is a major factor in the The cytotoxic effect of the extract was morbidity and mortality among cancer assessed using the MTT assay. The effect patients, which accounts for 90% of all of the extract on the attachment and cancer-related deaths. This is because of migration of HT-29 cells was assessed using the lack of effective therapeutic strategies the cell adhesion and wound healing assay, to completely prevent the dissemination respectively. of cancer cells from a primary tumour to other parts of the body. However, there RESULTS is a continued search for more effective Our results showed that the extract antimetastatic drugs. This search has now inhibited cell viability in both concentration- shifted towards plants, particularly those and time-dependent manner. The extract used to treat various ailments traditionally. also showed a concentration- and time- Recent studies have shown plants in various dependent inhibition of cell attachment genera to have anticancer properties and migration. including plants in the Momordica genus. CONCLUSION This genus consists of about 60 species, The extract inhibits migration and and only a few have been shown to possess attachment of colon HT-29 cancer cells, biological activities. in vitro. However, further studies will be OBJECTIVE conducted to assess the effect of the extract To investigate the in vitro antimetastatic on HT-29 invasiveness and angiogenesis. effects of Momordica balsamina crude acetone leaf extract on human colon HT-29 cancer cells.

139 THE ANTIMETASTATIC EFFECTS OF MOMORDICA BALSAMINA ON HT- 29 COLON CANCER CELLS 1K. Serala, 1L. Mampuru, 2S. Prince, 1V. Mbazima 1 University of Limpopo Department of Biochemistry, Microbiology and Biotechnology, Sovenga, 2 University of Cape Town, Department of Cell Biology, Observatory

BACKGROUND METHODS Cancer metastasis is a major factor in the The cytotoxic effect of the extract was morbidity and mortality among cancer assessed using the MTT assay. The effect patients, which accounts for 90% of all of the extract on the attachment and cancer-related deaths. This is because of migration of HT-29 cells was assessed using the lack of effective therapeutic strategies the cell adhesion and wound healing assay, to completely prevent the dissemination respectively. of cancer cells from a primary tumour to other parts of the body. However, there RESULTS is a continued search for more effective Our results showed that the extract antimetastatic drugs. This search has now inhibited cell viability in both concentration- shifted towards plants, particularly those and time-dependent manner. The extract used to treat various ailments traditionally. also showed a concentration- and time- Recent studies have shown plants in various dependent inhibition of cell attachment genera to have anticancer properties and migration. including plants in the Momordica genus. CONCLUSION This genus consists of about 60 species, The extract inhibits migration and and only a few have been shown to possess attachment of colon HT-29 cancer cells, biological activities. in vitro. However, further studies will be OBJECTIVE conducted to assess the effect of the extract To investigate the in vitro antimetastatic on HT-29 invasiveness and angiogenesis. effects of Momordica balsamina crude acetone leaf extract on human colon HT-29 cancer cells.

140 IN VITRO ANTIDIABETIC AND CYTOTOXICITY PROPERTIES OF COMMELINA BENGHALENSIS ACETONE EXTRACT AGAINST 3T3-L1 CELLS 1T. Tshidino, 1K.W. Poopedi, 1L.J. Mampuru, 1M.P. Mokgotho 1 Department of Biochemistry, Microbiology & Biotechnology, University of Limpopo, Sovenga

BACKGROUND chromatography will be used to analyse the Conventional antidiabetic drugs have phytochemical constituents in the extract. undesirable side effects, are not easily The viability of 3T3-L1 cells was evaluated accessible, and are expensive. As using the 3-(4,5-dimethylthiazol-2-yl)-2,5- such, there is a need to investigate diphenyltetrazolium bromide assay, and alternative antidiabetic treatments. the cellular and nuclear morphological Commelina benghalensis (C. benghalensis) features associated with apoptosis will be has been reported to possess antimicrobial, assessed using acridine orange/ethidium antidiarrheal and cytotoxic activities. The bromide-dual staining. The acetone extract antidiabetic properties of C. benghalensis of the plant will be evaluated for its glucose have also been reported. However, there is uptake and utilisation of the ATP molecule a paucity of information on this aspect of ability using colometric assays. the plant. CONCLUSIONS OBJECTIVE In this study, we will analyse the To investigate the antidiabetic and effectiveness of the extract on the glucose cytotoxicity properties of the acetone and ATP uptake utilisation. Furthermore, extract of C. benghalensis on 3T3-L1 cells. the basic components determined in the extracts will infer the activity of the extract. METHODOLOGY Commelina benghalensis will be extracted using acetone. The High-performance liquid

141 SAMRC MID-CAREER SCIENTIST PROGRAMME (MCSP)

MS PHILISTIA JOSHUA – PROGRAMME ADMINISTRATOR

142 PROTEOMIC ANALYSIS OF GEOMETRICALLY AND ETHNICALLY CLASSIFIED HUMAN HAIR IN A SOUTH AFRICAN COHORT 1H. Adeola, 1N. Mehlala, 1N. Khumalo 1 Hair and Skin Research Laboratory, Division of Dermatology-Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa

BACKGROUND RESULTS As well-established, hair is mostly composed Using various proteomics bioinformatics of keratins and keratin-associated proteins. pipelines, we have identified over 450 Hence, an in-depth understanding of the protein groups (FDR=0.01) in the South physiological proteome of hair is a potential African hair proteome. Proteins identified treasure-trove for identification of non- included: keratins, keratin-associated invasive biomarkers for various diseases. proteins, desmosomes, and histone However, there has been a few bottlenecks proteins, inter alia. Functional pathway in the large-scale identification of the full analysis of high-ranking proteins showed complement of proteins in human hair enrichment for skin, epidermal and tissue samples. Not the least, differences in the development as well as intermediate physiological proteome of men of different filament organisation. ethnic origin are poorly researched. CONCLUSION OBJECTIVES In this study, we validate the fact that The objective of this study is to characterise medical research needs an urgent shift away the physiological hair proteome of various from racial classification and embraces a ethnicities within a South African cohort. more objective classification of human hair. Also, the established physiological METHODS hair proteome could potentially serve as We carried out label-free, shotgun a template for the identification of disease proteomics analysis on various ethnically biomarkers. and geometrically classified hair samples collected from a heterogeneous population in the Western Cape of South Africa.

143 THE ROLE OF STEM CELLS IN THE PATHOGENESIS OF SCARRING ALOPECIA 1M. Alkelani, 1H. Adeola, 1N. Khumalo 1 Faculty of Health Science, Division of Dermatology, Department of Medicine, University of Cape Town

BACKGROUND alopecia. Also, to find out if the bulge stem Scarring alopecia (also called cicatricial cell biology can be used to monitor the alopecia) is a type of alopecia which progression of or classify scarring alopecia. results in permanent hair loss, which can be caused by several factors, including METHODS systemic conditions such as scleroderma A biopsy will be obtained from scarring and discoid lupus. The hair follicles are alopecia patients at the hair clinic of Groote destroyed completely, and the hair does Schuur Hospital, Cape Town. Proteomic not grow again. The disease affects analysis will be done by using scanning males and females and is more common electron microscopy, MALDI imaging among adults than in children. There mass spectrometry and laser capture were significant clinical and fibroblastic microdissection. Also, Flow Cytometry inflammatory phenomena in the type analysis will be used to isolate and identify of hair loss, and the term “nodal hair the stem cells population. loss” has been suggested. Stem cells are RESULTS regenerative cells, with the unique ability We expect to get a better understanding of to develop into specialised cell types in the role of stem cells during the stages of the body. However, the pathogenetic scarring alopecia and to identify molecular mechanism of scarring alopecia remains changes. unclear, as do what the roles of stem cells are in these lesions. CONCLUSION The success of this study will give a clearer OBJECTIVES understanding of the role of stem cells To determine if the hair follicle bulge stem in scarring alopecia. Also, it would help cells undergo structural and molecular identify diagnostic and prognostic stem- changes during the progression of scarring cell biomarkers of scarring alopecia.

144 IS THERE AN ASSOCIATION BETWEEN FRONTAL FIBROSING ALOPECIA AND SUNSCREEN ACTIVES? 1K. Chabaesele, 1H. Adeola, 1M. Lebeko, 1N. Khumalo 1 Health Sciences, Dermatology, Hair and Skin Research Laboratory, University of Cape Town

BACKGROUND (CCK8) was used to measure the cytotoxicity Frontal fibrosing alopecia (FFA) is a effect of the actives on the cells. Metabolic subtype of lymphocytic primary scarring phenotype switch of the treated cells was alopecia associated with progressive, also analysed using Seahorse bioanalyzer. inflammation of hair follicles and permanent replacement by fibrous tissue. RESULTS Clinically FFA is characterised by a band- The human keratinocyte cell line and like recession of the frontal hairline which FFA primary fibroblasts show varying may be associated with eyebrow loss and susceptibility to sunscreen actives, with facial hyperpigmentation. Since the report zinc oxide being most cytotoxic. Real-time in postmenopausal women, the number extracellular flux analysis indicates that of published cases initially remained low. zinc oxide induces an aerobic phenotype However, in the last decade, there has been switch only on keratinocytes. Titanium an exponential increase in cases which dioxide induces an energetic phenotype include younger women and men (largest switch in both cell types, increasingly more study 355 patients). The psychopathology dramatic in fibroblasts from FFA edge and from FFA is significant and the cause scar samples. Chemical sunscreen actives unknown. show a negligible effect on the energy phenotype of both cell types. OBJECTIVE To evaluate cytotoxicity and bioenergetics CONCLUSIONS of sunscreen actives in a keratinocyte cell Zinc oxide is the most cytotoxic and line and site-specific fibroblasts from FFA with titanium dioxide exhibit significant bioenergetic changes compared to patients. chemical sunscreen actives on mono-layer METHODS cells. The effect of physical sunscreen Two cell types, human keratinocytes and actives (traditional and nano-particles) FFA-derived fibroblast, were exposed warrants further investigation on more to five common sunscreen actives, complex (closer-to-real-life) in vitro and ex titanium dioxide, zinc oxide, octinoxate, vivo 3D-organ culture models. benzophenone-4 and Padimate O, over 24 hours. Thereafter, the cell counting kit-8

145 INTERDEPENDENCE BETWEEN GEOMETRIC, TENSILE AND CHEMICAL BOND BEHAVIOURS OF UNTREATED CURLY HAIR FIBRES 1E. Cloete, 1N. Khumalo, 2J. van Wyk, 1M. Ngoepe 1 Hair & Skin Research Laboratory, Dermatology, University of Cape Town, Cape Town, South Africa; 2 Textile Research Institute, Princeton, NJ 08540, USA

BACKGROUND medium strain regions showed a sequence Until now, an accurate understanding of of distinct horizontal, exponential and the dynamics between the fibre’s inherent linear patterns for curly fibres, but an geometric, mechanical and biological absence of the horizontal and exponential characteristics is deficient, affecting the sections for low-curl fibres. Based on reliability and robustness of hair data. these regions, a 3-component constitutive There is also insufficient scientific clarity on equation was developed, describing fibre deviations of curly hair from characteristic tensile strength, which, until now, was fibre behaviour. assumed to be calculable from the linear region (via Young’s modulus) only. The OBJECTIVE diverse nature of the components (i.e. To gain an accurate understanding of the chemical, viscous, elastic) demonstrated interrelationships between diverse fibre the dynamic complexity of curly fibres. attributes of curly fibres. Hydrogen bonds, previously thought as an insignificant distinctive fibre strength METHODS contributor, were shown to underwrite Research tools included tensile, geometric, intrinsic curvature permanence and to be image, spectroscopic assessments, subject to mechanical fragility during fibre regression modelling and multivariate preparation for tensile measurements. statistical analysis. Fibre attributes, assessed Based on de facto tensile measurement individually and comparatively, included methods, curly fibres are currently length, diameter, cross-sectional area, considered to have a lower tensile strength curl index, curl peaks, tensile behaviour in than low-curl fibres. toe- and elastic regions, and absorbance behaviour. CONCLUSION Although confirmation is required through RESULTS larger studies, findings strongly suggest Through the findings of this research, it improved reliability and robustness of was shown that, that there is an additional fibre data by considering the parameters material property (mechanical energy) explored in this study. associated with curly fibres, which is absent in non-curly fibres. Tensile patters in low-to-

146 THE USE OF HAIR TO DETECT AND MONITOR HYPERGLYCAEMIA – A PILOT STUDY 1S. da Silva, 1N. Khumalo, 2J. van Wyk, 1A. Spitaels, 1S. Delport, 1H. Nieuwoudt 1 Hair & Skin Research Laboratory, Dermatology, University of Cape Town, Cape Town, South Africa; 2 Textile Research Institute, Princeton, NJ 08540

BACKGROUND analysed using Fourier transform infrared- Hyperglycaemia results in debilitating attenuated total reflection (ATR-FTIR) complications. Therefore, it is vital for spectroscopy. Spectra were analysed with diabetics to monitor and control their SIMCA, Umetrics. blood-glucose levels between 7 and 9 mmol/L. Chronic estimates of glucose RESULTS control are obtained using glycated When ATR-FTIR spectra were analysed haemoglobin (HbA1c) valid for 8–12 weeks. using multivariate data analysis, orthogonal Since scalp hair grows at 1 cm per month projections to latent structures discriminant and comprises 65–95% protein, which is analysis models between spectra obtained subject to glycation, it could potentially be from the hair of diabetic participants and a useful non-invasive method of monitoring those from controls, show good separation chronic glycaemic control. and predictive ability. Partial least squares revealed a good correlation between hair OBJECTIVE FTIR spectra and participant HbA1c levels. To determine whether hair may be an The correlation varied between 0.8067 and alternative substrate for monitoring chronic 0.9296 depending on whether participants’ hyperglycaemia. hair was natural or had undergone various chemical cosmetic treatments. METHODS Scalp hair and blood samples (for HbA1c) CONCLUSIONS were collected from 46 diabetics with We demonstrated the potential ability to matched controls. Twenty-six adult cases distinguish between the hair of diabetics (30–70 years) and 29 controls (26–65 years), and controls including to predict HbA1c were recruited from the outpatient clinic at levels from hair using ATR-FTIR. These Groote Schuur hospital. Children recruited promising prospects for non-invasive from outpatient clinics at the Red Cross diabetes screening and long-term blood children’s hospital included 20 cases (7–18 glucose monitoring suggest greater years) and 17 controls (7–17 years). History insights into the timing and development of chemical hair treatment was recorded of diabetic complications. for each participant. Hair samples were

147 THE IDENTIFICATION OF NOVEL MICROBIAL SIGNATURES AS BIOMARKERS IN TRACTION ALOPECIA 1,2M. Gabier, 1H. Adeola, 1N. Mehlala, 1N. Khumalo 1 Hair and Skin Research Laboratory, Division of Dermatology, University of Cape Town; 2 Faculty of Applied Sciences, Cape Peninsula University of Technology

BACKGROUND OBJECTIVES Traction alopecia (TA) is a biphasic type Factors that govern the progression of of hair loss that can be described as non- TA from early to later stages is poorly scarring in its early stage. In this scenario, understood and no studies have been the stem cells can still be stimulated for done on this. Hence, it could be useful to regeneration of hair growth. However, if look at the potential roles of microbes in it progresses to a later stage it becomes TA, to better elucidate the mechanism of a scarring type in which the surrounding disease. tissue is replaced with fibrous tissue and the hair follicle is lost leading to baldness. METHODS People of every race may be affected by High-end targeted metaproteomic tools TA, while two South African studies showed will be used to identify potential microbial that 31.7% of women and 9.4% of children biomarkers for early detection and progress are affected by TA. A variety of hair traction monitoring of TA. and pulling forces that people do during RESULTS hair grooming, weaving, braiding, clipping With this research, the roles that micro- as well as binding hair in ponytails causes organisms play in TA will be better TA. This can be psychosocially traumatising, understood. More importantly, novel particularly in women, and may lead to protein sequences that are highly sensitive emotional distress, lack of confidence and and specific to TA can be used asa depression. When a pulling force is applied diagnostic tool for early disease detection to the hair, the pores open providing entry and will be identified. to the natural microflora. With a change of environment, the natural microflora CONCLUSION becomes pathogenic. The success of this research will create awareness of the dangers caused by chemicals and the application of force onto the hair.

148 THE STOP RHEUMATIC HEART DISEASE THROUGH AWARENESS RAISING, SURVEILLANCE, ADVOCACY, AND PREVENTION RESEARCH PROGRAMME: LONGITUDINAL STUDIES OF PRIMARY AND SECONDARY PREVENTION OF RHEUMATIC HEART DISEASE 1O. Kgasha, 1M. Nchabeleng, 1X. Khosa, 2H. Mabuza, 3M. Moshe, RHD team-SMU/UCT Departments of 1 Microbiology, 2 Family Medicine, 3 Paediatrics, Sefako Makgatho Health Sciences University & University of Cape Town

BACKGROUND also collected from the NHLS service Group A streptococcus (GAS) is responsible laboratory. Quantitative antimicrobial for a wide range of invasive and non- susceptibility tests were performed using invasive infections. Pharyngitis caused by E-test and Kirby-Bauer methods. Results GAS may trigger complications such as were interpreted using CSLI guidelines and acute rheumatic fever leading to rheumatic EUCAST. Emm typing was performed using heart disease (RHD) which continues to PCR by amplifying and sequencing the 5’ have high mortality and morbidity. Hence portion of the emm gene. GAS antigen the need to find intervention strategies such specificity will follow. as vaccines for control of GAS infection. RESULTS OBJECTIVES Seventy-two throat swabs were collected To establish surveillance of GAS pharyngitis from which 25% (18/72) GAS isolates were and validate a South African clinical recovered. In addition, 48 GAS isolates decision rule for treatment at selected were collected from the NHLS service clinics in the northwest of Pretoria. Also, laboratory. All isolates were susceptible to to determine the GAS antigen specificity all antibiotics tested with no MICs creeping of the human immune response following up. Thus far, 24 isolates have been typed, natural pharyngeal infection and to and ten emm types were found. Emm 92.0, evaluate the homing receptor expression which is a vaccine type, is the most found of intra-lesional valve T cells for skin versus emm type. oral mucosa. CONCLUSIONS METHODS All isolates were susceptible to the routinely Throat swabs from patients presenting used antibiotics for GAS treatment. Emm with pharyngitis to selected clinics were typing shows that 50% of the isolates collected for GAS isolation. Blood serum circulating in this region are not covered in was collected from patients with culture- the 30-valent vaccine underdevelopment. confirmed GAS isolates for immunological The study is ongoing. response investigation. GAS isolates were

149 DIFFERENTIAL GENOMIC PROFILING FOR STAGING AND DIAGNOSIS OF TRACTION ALOPECIA: A PILOT STUDY 1,2H.A. Adeola, 3P.S. Magangane, 1,2N. Mehlala, 1R.M. Ngwanya, 1,2N.P. Khumalo 1 Division of Dermatology, Department of Medicine, Faculty of Health Sciences and Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa; 2 Proteomics Pathology and Molecular Imaging Group, Hair and Skin Research Laboratory, Groote Schuur Hospital, Cape Town, South Africa; 3 Department of Anatomical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa

BACKGROUND using a Qiagen RNA extraction kit. The Traction alopecia (TA) is a type of abnormal extracted RNA of each sample was reverse- hair loss caused by excessive amounts of transcribed into cDNA using the Qiagen tension being placed on hair shafts. TA has cDNA Synthesis RT2 First Strand kit. The two phases, the early and late stage. Early cDNA was sequenced on the Quant Studio stage TA is reversible and non-scarring, 6 Flex analyser RT-PCR and the resulting while late-stage TA is irreversible and leads sequences loaded and analysed on Qiagen to scarring and permanent hair loss. Recent GeneGlobe Array Finder software. We did studies have shown that treatment of TA is this to identify the gene panels that match only successful if the cause of the condition the cDNA targets of the two groups being is recognised early enough and the patient analysed. is willing to discontinue the styling practice causing the traction. General population RESULTS data have been reported in South African The student t-test gave a p-value of female and child cohorts. In this population, 0.05, showing that the two groups were mild to moderate TA was dominant in significantly different. The gene panel 31.7% of women and between 8.6% and yielded a total of 89 genes which were 21.7% of children, ages 6–15 years. differentially expressed between the two groups. OBJECTIVES Our focus was to identify differentially CONCLUSION expressed genes and to compare the In this study, we successfully demonstrated genomic signatures of the two stages of TA. a difference in the genomic signatures of early- and late-stage TA. METHODS RNA was extracted from two early- and two late-stage scalp FFPE tissue samples

150 IMPACT OF NYAOPE ON PHYSICAL HEALTH AND ORGAN FUNCTIONS 1A. Khine, 2K. Mokwena, 3V. Moodley Departments of 1 Chemical Pathology; 2 Public Health; 3 Haematology, Sefako Makgatho Health Sciences University

BACKGROUND haematological parameters were assessed Unique to the mostly lower socio-economic from blood samples. All biochemistry tests youth who live in South African townships, were analysed on the Abbott Architect Nyaope is a very addictive novel or cocktail ci8200 and haematological tests on the psychoactive substance of abuse. In a ADVIA® 2120i System. previous study, we identified caffeine, other drugs of abuse which included stimulants, RESULTS sedatives, antibiotics, and antiretroviral Compared to normal ranges, significant drugs, as components of the substance. differences were found in the serum Typical complaints of Nyaope users include electrolytes, anion gap, liver enzymes, severe abdominal cramps, tremendous gonadal hormones and differential blood drowsiness, vomiting and sometimes counts, while the renal function tests did not diarrhoea. However, with the use of Nyaope show significant differences. Of the Nyaope progressive weight loss, which is associated users, 86.7% (n=85) showed abnormalities with decreased appetite, emanates. in the range of laboratory tests performed, with the number of participants with OBJECTIVES specific organ dysfunctions ranging from To explore the impact of Nyaope on 10.2% to 31.6%. physical health and organ function. CONCLUSIONS METHODS Nyaope compromises physical health The sample size consisted of 98 Nyaope and organ functions on selected cases. users who were recruited from Soshanguve, Conducting further studies on occult Mabopane and Ga-Rankuwa. Demographic infections and possible bone marrow data were collected using a self- suppression is recommended. administered questionnaire. Liver, renal, thyroid and gonadal functions as well as

151 MOLECULAR APPROACHES FOR CHARACTERISATION OF CICATRICIAL ALOPECIA 1T. Sikhakhane, 1H. Adeola, 1N. Khumalo 1 University of Cape Town, Hair and Skin Research Laboratory, Groote Schuur Hospital

BACKGROUND using state-of-the-art, label-free, mass The term ‘‘cicatricial alopecia’’ comprises a spectrometry. Furthermore, top ranking group of hair-loss disorders characterised potential biomarkers will be validated by permanent destruction of the hair follicle. by various genomic and proteomic Although the cause and pathogenesis of techniques including histopathology, these conditions remain poorly understood, immunohistochemistry, molecular imaging, it is known that ultimately the follicular units PCR and sequencing. are replaced by fibrous tissue leading to progressive and permanent scalp hair loss. RESULTS This condition affects males and females The success of the study will result in and can often lead to several psychological the development of reliable and robust disturbances such as anxiety, depression, diagnostic biomarkers and a more elegant low self‐esteem, feelings of loneliness, and classification system for the different types social isolation. of scarring alopecia.

OBJECTIVES CONCLUSIONS In this study, we aim to identify novel Acquiring this vast information will molecular diagnostic and therapeutic contribute to closing the knowledge gap approaches/biomarkers for better disease in the molecular pathogenesis of PCA classification as also to understand the and thus improve the management of this aetiology and molecular pathogenesis of condition that results in distress, depression primary cicatricial alopecia (PCA) using and psychological disturbances, particularly proteomic and genomic methods. in females. The success of this study will not only benefit South Africa but the whole METHODS world, as this disease is not geographically We will identify potential diagnostic and limited. therapeutic biomarkers of various PCA

152 SAMRC SCHOLARSHIP BENEFICIARIES WHO HAVE COMPLETED THEIR DEGREES (MASTERS/DOCTORATE) IN THE PAST 12 MONTHS: BY PROGRAM

MS. COLLEEN VAN WYK ADMINISTRATIVE ASSISTANCE (RCD)

153 SAMRC CLINICIAN RESEARCHER DEVELOPMENT (M.D PHD) PROGRAMME Name & Institution Research Topic Supervisor Surname Dr Andre Rose University of Radiation-induced lens changes and Prof William Free State development of a radiation frameworks Raire for interventionists Dr Goodman University of Pilot testing models of task shifting for the Prof Dan Stein Sibeko Cape Town care of serious mental illness in South Africa Dr University of Assessing the reliability and validity of Prof Lee Wallis Mohammed Cape Town the South African triage scale in low to Dalwai middle income setting Dr Aneesa University of Indoor air pollution and tobacco smoke Prof RP Gie Vanker Cape Town exposure in a South African birth cohort Dr Kwazi University of The effect of HIV infection on the Prof Alain Ndlovu KwaZulu-Natal management of renal failure among Guy Honore patients undergoing peritoneal dialysis Assounga Dr Vuyani University of The role of syntiocytotrophoblast Prof Manu Mhlomi Oxford (UK) extracellular vesicles in the regulation Vatish of cardiovascular physiology in normal pregnancy and preeclampsia Dr Alex Stellenbosch Default mode network in social Prof James Doruyter University anxiety disorder: correlations with Warwick neuropsychiatric measures of social cognition and dopaminergic function SAMRC INTERNSHIP SCHOLARSHIP PROGRAMME (ISP) Sibusiso University of Characterization of mycobacterial Prof Bavesh Senzani (PhD) Witwatersrand amidases and their role in bacterial Kana growth and physiology Nicola University of Characterization of the electron transport Prof Bavesh Cardoso (PhD) Witwatersrand chain in mycobacteria Kana Neo Mokhesi University of The investigation of miRNA expression in Dr C Dandara (MSc) Cape Town thyroid carcinoma among South African patients Kebareng Sefako Molecular characterization of rotavirus Dr Seheri and Rakau (MSc) Makgatho infection in children attending Dr George Dr Gedezho Health Science Mukhari academic hospital and Oukasie University Primary Healthcare and their association with histo blood group antigen profile

154 NATIONAL HEALTH SCHOLARSHIP PROGRAMME (NHSP) Zamasomi University of A Study of transgendered people access TBC Luvuno (PhD) KwaZulu-Natal and management of sexual reproduction Jenny Coetzee University of Factors affecting HIV infection amongst Prof G Gray, (PhD) Witwatersrand female sex workers in Soweto, South Co-Supervisor Africa Prof Rachel Jewkes Ferdinand University of A realist evaluation of the antiretroviral Prof Brian Mukumbang the Western treatment adherence club programme van Wyk, Co (PhD) Cape in the metropolitan area of the Western Supervisor Cape Province, South Africa Prof Bruno Marchal and Dr Sara van Belle Robyn University of A randomized control trail comparing Dr Gretchel, Meissner (PhD) Cape Town occupational therapy interventions that Co Supervisor aim to improve developmental outcomes Ramugondo for HIV-positive children (aged 6 months – 5 years) SAMRC RESEARCH CAPACITY DEVELOPMENT INITIATIVE POST-GRADUATE SCHOLARSHIP PROGRAMME Ms Matume University of Diversity in APOBEC3 and CCR5 host Prof Bessong (PhD) Venda genes and HIV-1 in a South African population Ms University of Determinants of adherence to HAART in Prof Bessong Tanganedzani Venda a prospective HIV cohort in South Africa (MSC) Ms Sangweni University of The Cardioprotective Effect of Lanostery Dr Rabia (MSc) Zululand Triterpene from protorhus Longifolia on Johnson H9c2 Cardiomyoblasts Ms Malemela University of Investigation of the probable anti-cancer Dr VG (MSC) Limpopo effects of the crude methanol extract Mbazima of Dicerocaryum Senecioides, (Klotzch) J.Abels, leaves on cervical Hela cancer cells

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