Research Health Sciences Research Review│May 2023

WITS HEALTH SCIENCES RESEARCH REVIEW

Wits scientists in the team that identified a third case of HIV infection cured by stem cell transplantation

Wits & U S Congress celebrate 20 years of PEPFAR

Health and nutrition claims for infant formula

Patent Urachus with Posterior Urethral Valves

Interpreting eGFR in people of black ethnicities

Highlighting the impact of social dynamics on the health and well-being of individuals and the wider population

WHAT'S HAPPENING

Mentor current students towards employability

The Microbiome Mapping Initiative establish a national microbiome profiling platform

Editorial – Research Newsletter

The Newsletter is an opportunity for us to present retrospective research article collections to showcase research excellence from the different disciplines in the Faculty, celebrate staff awards and achievements, highlight upcoming events and share general information

I am pleased to take this opportunity to congratulate a number of researchers who received prestigious awards for their outstanding contributions to the advancement of research in the period March to May 2023 Firstly, Professor Bavesh Kana who was awarded a Gold Medal for Tuberculosis Molecular Diagnosis Secondly, both Professor Bavesh Kana and Professor Lynn Morris were appointed to the National Advisory Council on Innovation Thirdly, Professor Helen Rees who was conferred with a degree of Doctor of Laws (LLD) by Rhodes University Lastly, we congratulate our Wits’ young human genetics scientists who did exceptionally well at the Young Investigators Forum held in Cape Town in February 2023

In this issue, we also feature a number of research articles published by some of our researchers in the Faculty. From the activities displayed in this Newsletter, it is evident that research is alive and thriving in the Wits Faculty of Health Sciences!

Well done to all for your exceptional contributions and hard work!

Contacts

Faculty of Health Sciences, University of the Witwatersrand

www wits ac za/health

Do you want your research work to be featured?

For staff, email: didi.mmatladi@wits.ac.za

Alumni submission, email: alumni healthsciences@wits ac za

Professor Maria Papathanasopoulos Assistant Dean: Research, Innovation and postgraduate Support Wits Faculty of Health Sciences

Didi Mmatladi Nomfundo Sibiya

Research in high-impact factor journals:

Efficacy of pyriproxyfen-pyrethroid

LLINs and chlorfenapyr-pyrethroid

LLINs for malaria control in Benin

Lancet (IF - 202.731)

New classes of long-lasting insecticidal nets (LLINs) combining mixtures of insecticides with different modes of action could put malaria control back on track after rebounds in transmission across sub-Saharan Africa. This study evaluated the relative efficacy of pyriproxyfen-pyrethroid LLINs and chlorfenapyrpyrethroid LLINs compared with standard LLINs against malaria transmission in an area of high pyrethroid resistance in Benin.

Interpretation

Over 2 years, chlorfenapyr-pyrethroid LLINs provided greater protection from malaria than pyrethroid-only LLINs in an area with pyrethroidresistant mosquitoes Pyriproxyfen-pyrethroid LLINs conferred protection similar to pyrethroid-only LLINs. These findings provide crucial second-trial evidence to enable the WHO to make policy recommendations on these new LLIN classes This study confirms the importance of chlorfenapyr as an LLIN treatment to control malaria in areas with pyrethroid-resistant vectors However, an arsenal of new active ingredients is required for successful long-term resistance management, and additional innovations, including pyriproxyfen, need to be further investigated for effective vector control strategies.

*Read the full study

COVID-19 infection, reinfection, and the transition to endemicity

Lancet (IF - 202,731)

Understanding the protection conferred by previous infection against repeat infection, illness, and severe disease is key to projecting the future epidemiology of COVID-19 and to guiding vaccine policy decisions In The Lancet, The COVID-19 Forecasting Team report data from a systematic review and meta-analysis of 65 studies from 19 different countries estimating the reduction in COVID-19 risk among individuals with previous SARS-CoV-2 infection, compared with those without previous infection.

This analysis is particularly important following the emergence of the omicron variant in late 2021, with rapid spread globally Currently, in most parts of the world, COVID-19 is dominated by different omicron sublineages, with the ongoing emergence of new sublineages demonstrating the importance of potential immune escape

The COVID-19 Forecasting Team found a high level of protection against reinfection and symptomatic disease for ancestral, alpha, beta, and delta variants (mean pooled estimate >82%) but substantially lower protection (approximately 45%) for the omicron BA 1 variant Protection against severe disease was high for all variants evaluated (>85% at 40 weeks)

*Read the full article

Wits Researchers involved (WRIM): Immo Kleinschmidt

Wits researchers involved: Cheryl Cohen

Research in high-impact factor journals:

Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A

New England Journal of Medicine (IF - 176,08)

Patent Urachus with Posterior Urethral Valves

Valoctocogene roxaparvovec delivers a B-domain–deleted factor VIII coding sequence with an adenoassociated virus vector to prevent bleeding in persons with severe hemophilia A

Methods

An open-label, single-group, multicenter, phase 3 trial was conducted in which 134 men with severe hemophilia A who were receiving factor VIII prophylaxis received a single infusion of 6×1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight

Results

At week 104, a total of 132 participants, including 112 with data that were prospectively collected at baseline, remained in the study. The mean annualized treated bleeding rate decreased by 84.5% from baseline (P<0 001) among the participants The risk of joint bleeding was estimated among the trial participants; at a transgene-derived factor VIII level of 5 IU per deciliter measured with chromogenic assay, it was expected that participants would have 1.0 episodes of joint bleeding per year

Models of the risk of joint bleeding suggest that the relationship between transgene-derived factor VIII activity and bleeding episodes is similar to that reported with the use of epidemiologic data for persons with mild-to-moderate hemophilia A

*Read the full article

A 1-month-old boy was transferred to a tertiary care hospital for the management of obstructive uropathy. He had initially been brought to a local hospital for progressive abdominal distention At the local hospital, laboratory studies had shown kidney injury, and ultrasonography of the abdomen showed a thickened bladder wall, ascites, hydronephrosis of both kidneys, and a perinephric collection around the left kidney He was subsequently transferred for further care.

On arrival at the tertiary care hospital, the physical examination was notable for a distended abdomen, reducible umbilical hernia, and rash on the lower abdomen When the abdomen was palpated, urine flowed from the umbilicus (video) A voiding cystourethrogram howed a dilated posterior urethra, bladder diverticula, and vesicoureteral reflux on both sides A diagnosis of posterior urethral valves was made Posterior urethral valves congenital obstructing membranes in the lumen of the urethra are a common cause of urinary tract obstruction in male infants. In severe cases, retrograde accumulation of urine can result in vesicoureteral reflux, bladder diverticula, urinomas, urinary ascites, and a patent urachus all of which were seen in this case Urachus ligation, urinoma drainage, urethral valve ablation, and a vesicostomy with later closure were performed. During 2 years of subsequent follow-up, the patient’s development and kidney function remained normal

*Read the full article

Wits researcher involved: Johnny Mahlangu

New

Wits researcher involved (Baragwanath Hospital): Karen Petersen, Derek Harrison

Research in high-impact factor journals:

Health and nutrition claims for infant formula: International cross-sectional survey

British Medical Journal (IF - 96,21)

Results

757 infant formula products were identified, each with a median of two claims (range from 1 (Australia) to 4 (US)), and 31 types of claims across all products

Of 608 products with ≥1 claims, the most common claim types were "helps/supports the development of brain and/or eyes and/or nervous system", "strengthens/supports a healthy immune system, and "helps/supports growth and development".

Wits Researchers involved (WDGMC): Lindsay

Archibald-Durham

This research is an international cross-sectional survey that set out to review available health and nutrition claims for infant formula products in multiple countries and to evaluate the validity of the evidence used for substantiation of claims.

Setting

Public-facing and healthcare professional-facing company-owned or company-managed formula industry websites providing information about products marketed for healthy infants delivered at full term in 15 countries: Australia, Canada, Germany, India, Italy, Japan, Nigeria, Norway, Pakistan, Russia, Saudi Arabia, South Africa, Spain, the United Kingdom, and the United States in 2020-22.

Main outcome measures

Number and type of claims made for each product and ingredient References cited were reviewed and the risk of bias was assessed for registered clinical trials using the Cochrane Risk of Bias tool, and for systematic reviews using the Risk Of Bias in Systematic Reviews tool

41 groups of ingredients were associated with ≥1claims, but many claims were made without reference to a specific ingredient. The most common groups of ingredients cited in claims were long-chain polyunsaturated fatty acids; prebiotics, probiotics, or synbiotics; and hydrolysed protein 161/608 (26%) products with ≥1 claims provided a scientific reference to support the claim-266 unique references were cited for 24 different claim types for 161 products The reference types most frequently cited were clinical trials and reviews 28% of referenced clinical trials were registered, 14% prospectively 58 claims referred to 32 registered clinical trials, of which 51 claims related to a randomised comparison. 46 of 51 claims (90%) referenced registered clinical trial outcomes at high risk of bias, and all cited systematic reviews and pooled analyses, carried a high risk of bias.

Conclusions

Most infant formula products had at least one health and nutrition claim Multiple ingredients were claimed to achieve similar health or nutrition effects, multiple claims were made for the same ingredient type, most products did not provide scientific references to support claims, and referenced claims were not supported by robust clinical trial evidence

*Read the full article

Research in high-impact factor journals:

Interpreting an estimated glomerular filtration rate (eGFR) in people of black ethnicities in the UK

British Medical Journal (IF - 96,21)

was 75 mL/min/1 73 m2 (serum creatinine 114 μmol/L), and urinary albumin creatinine ratio (ACR) was 2 mg/mmol. His chronic kidney disease (CKD) classification was G2A1 (low risk of adverse outcomes)

Today, his blood pressure averaged 145/90 mm Hg across three readings. He has been taking 5 mg amlodipine regularly. His eGFR is calculated without an ethnicity adjustment to be 58 mL/min/1 73 m2 (serum creatinine 140 μmol/L) Clinical examination is unremarkable A urine dipstick analysis shows no blood and 2+protein, and a urinary ACR identifies progression to macroalbuminuria (37 mg/mmol). An ultrasound scan of the urinary tract, electrocardiogram, and prostate-specific antigen (PSA) tests are normal

Case outcome

What you need to know:

More people of black African or black Caribbean ethnicity will meet the criteria for chronic kidney disease (CKD) diagnosis when ethnicity adjustment for estimated glomerular filtration rate (eGFR) calculation is not used

Classification and clinical coding of early CKD (including asymptomatic proteinuria) in primary care (including re-calculation of eGFR without adjustment) enables healthcare providers to systematically target interventions that aim to reduce cardiovascular events and progression to end-stage kidney disease (ESKD)

Measure albumin creatinine ratio in addition to eGFR to identify patients at the highest risk of adverse events (cardiovascular disease and ESKD)

A 37-year-old man attends his GP for a review of his blood pressure He was born in the UK, and his parents are from Nigeria He was last reviewed three years ago, soon after being diagnosed with essential hypertension, and had been given lifestyle advice and prescribed amlodipine 5 mg daily An estimated glomerular filtration rate (eGFR) adjusted for ethnicity

After reassessment of the patient’s eGFR without adjustment for ethnicity, his GP explained that he has chronic kidney disease with a code of G3bA3, which is associated with a very high risk of adverse outcomes such as cardiovascular disease This re-coding puts a clear focus on optimising his care to reduce the progression of renal disease and cardiovascular risk. No confirmatory test was required, as risk criteria were met with raised ACR and a history of hypertension Based on the Kidney Failure Risk Equation (KFRE), his risk of kidney failure in the next five years is 1.77% (considered low in patients with CKD 3).

Recommended management of stage 3 CKD according to NICE guidelines includes optimal reninangiotensin-aldosterone system (RAAS) blockade, optimisation of blood pressure control (<130/80 mm Hg for proteinuric CKD), initiation of a statin, and a sodium-glucose co-transporter-2 (SGLT-2) inhibitor

A patient’s perspective

" I believe that the removal of the ethnicity adjustment for the calculation of eGFR is a positive step forward in building trust in the management of care for patients of black Caribbean and black African heritage I strongly believe that the care of each patient should be personcentred and personalised so that the care of each patient is led by their individual needs and not solely by their ethnicity..." - Dee

Moore

*Read the full article

Wits Researchers involved (WDGMC): June Fabian

Research in high-impact factor journals:

Epidemiological and clinical characteristics of patients with monkeypox in the GeoSentinel Network: a cross-sectional study

Lancet Infectious Diseases (IF - 71,42)

The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. This study aimed to describe the epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection.

Methods

Descriptively analysed data was used for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. A descriptive analysis was made on epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm3 or 500 cells per mm3 and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination

Findings

226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18–68; IQR 32–

43) Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm3 (range 36–1659; IQR 500–885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1–8) Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to the hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control.

No deaths were reported Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0 002), perianal rash or lesions (p=0 03), and a higher rash burden (median rash burden score 9 [IQR 6–21] for patients with HIV vs median rash burden score 6 [IQR 3–14] for patients without HIV; p<0 0001), but no differences were identified in the proportion of men who had severe illness by HIV status

Interpretation

Clinical manifestations of monkeypox infection differed by HIV status Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact.

*Read the full study

Wits Researchers involved: Albie de Frey

Research in high-impact factor journals:

Towards functional improvement of motor disorders associated with cerebral palsy

Publication Journal: Lancet Neurology (IF - 59,93)

from 1,6 to 3,4 per 1000 livebirths, making cerebral palsy the most important cause of major motor impairment in childhood. The range in prevalence reflects the differences between high-income countries and low-income and middle-income countries Most population-based registers in highincome countries (mainly Australia and countries in Europe) have reported a decline in birth prevalence since the mid-2000s, which probably relates to improvements in public health and prenatal and perinatal care

Conclusions and future directions

A multidisciplinary and integrative approach that considers the inseparable link of motor behaviour with somatosensory impairments, cognition and learning, pain, mental health, social aspects, and quality of life is crucial in the management of people with cerebral palsy, ensuring meaningful outcomes throughout the lifespan Cerebral palsy is a heterogeneous condition and clinical practice suggests that a universal approach is inadequate.

Wits Researchers involved: Gillian Saloojee

Cerebral palsy is a lifelong neurodevelopmental condition arising from non-progressive disorders occurring in the fetal or infant brain. Cerebral palsy has long been categorised into discrete motor types based on the predominance of spasticity, dyskinesia, or ataxia.

Although cerebral palsy is permanent, function changes across the lifespan, indicating the importance of interventions to improve outcomes in motor disorders associated with the condition Mounting evidence exists for the inclusion of several interventions, including active surveillance, adapted physical activity, and nutrition, to prevent secondary and tertiary complications Avenues for future research include the development of evidence-based recommendations, low-cost and high-quality alternatives to existing therapies to ensure universal access, standardised cerebral palsy registers to harmonise epidemiological and clinical information, improved adult screening and check-up programmes to facilitate positive lived experiences, and phase 3 trials for new interventions

Epidemiology

The global birth prevalence of cerebral palsy ranges

People with cerebral palsy have individual needs and priorities, also depending on the stage of life

Therefore, treatment goals should always be tailored to address these needs and what individuals and their families deem relevant and meaningful Regarding a family-centred approach to services, the most important aspects rated by parents are the provision of specific information about their child’s therapy and assessment results, and coordinated and comprehensive care for the child across services

This Review has highlighted the many available options, and more therapeutic and technological advancements are foreseen. At the same time, advocacy efforts are increasing to ensure that societal and access barriers are addressed Nevertheless, despite the excitement about remarkable progress, decision-making in clinical practice (ie, establishing which treatment, of all those available, is best for an individual with cerebral palsy) remains challenging Ultimately, managing cerebral palsy should be aimed at achieving the best motor and functional outcomes that will support each individual achieve their goals throughout life

*Read the full study

Two leading Wits scientists appointed to National Advisory Council on Innovation

Professor Lynn Morris and Professor Bavesh Kana will advise government on how to harness and grow innovation.

Professor Lynn Morris is Deputy Vice-Chancellor for Research and Innovation at Wits, while Professor Bavesh Kana is Director of the Department of Science and Innovation/National Research Foundation (DSI/NRF) Centre of Excellence for Biomedical TB Research.

Another Witsie in a leadership role at the Council is acting CEO of NACI, Dr Mlungisi Cele, who also serves on the Wits Council on appointment by the Department of Higher Education and Training.

The members of NACI (other than the CEO and the officer from the Department of Trade and Industry) are appointed in their personal capacities due to their outstanding achievement in any field of science and technology, or in the context of innovation, special knowledge, experience and insight into the role and contribution of innovation, in promoting and achieving national and provincial objectives

As NACI members, Morris and Kana thus do not represent Wits University specifically Rather, Morris represents higher education and Kana innovation In their personal capacities, they will provide a high-level view of innovation nationally, advise on innovation priorities, and expenditure

A National Research Foundation A-rated scientist, Morris is internationally recognised with demonstrable experience in research management and leadership. She was previously the interim Executive Director of the National Institute for Communicable Diseases (NICD) where she led the NICD through the listeria outbreak of 2017/18 and the Covid-19 pandemic from 2020. She has published some 270 journal articles, 11 book chapters, registered five patents and 11 scientific opinions She has consistently been included in the Web of Science’s most highly cited researchers in the world.

South Africa doesn’t fare well in innovation indicators Zero point 62 percent of our GDP goes into research and development in South Africa, says Morris.

NACI demonstrates that government values science, technology, and innovation and it’s very important to have that buy-in

“South Africa doesn’t fare well in innovation indicators. Zero point 62 percent of our GDP goes into research and development in South Africa,” says Morris “NACI demonstrates that government values science, technology, and innovation and it’s very important to have that buy-in.”

Zero point 62 percent is the 2019 figure in the South African Science, Technology and Innovation Indicators report (STI Indicators report, pg. 29), which NACI produces as a tool to monitor the National System of Innovation (NSI)

The report compares South Africa’s performance with selected countries and aims to identify relative strengths and weaknesses of the national research and innovation system and inform priorities to improve innovation performance

The Indicators report is influenced by the South African Innovation Scorecard and the NACI Monitoring and Evaluation Framework, as well as the expansive impact of the Covid-19 pandemic

According to the Indicators report,

Due to the prolonged Covid-19 pandemic the South African economic growth has declined with consequent negative impact on the NSI The gross expenditure in research and development [GERD] as a percentage of growth domestic product has declined to 0 62%, which is a worrying trend regarding the 1 5% target

As a NACI member, Morris can tap into different networks to gauge where South Africa is nationally and globally Morris says there was a big push on innovation during Covid-19 and NACI now is “about introducing technology to grow the economy ”

Such technologies include patents and the report shows that, in 2020, South Africa ranked below all four of the BRICS group of countries in Rankings in Patent Applications per Million Inhabitants Furthermore, South Africa also ranked lower than India for the first time in a decade (STI Indicators report, pg 33)

Fortunately, Professor Bavesh Kana – who researchers tuberculosis (TB) – is no stranger to successful patent applications The introduction of technology that tests for TB using molecular diagnostics was a game changer for national TB programmes This tech increased access to TB testing, which then improved diagnosis and treatment, and ultimately inhibited further infection

However, when the World Health Organization endorsed this molecular diagnostic test, there was no quality assurance in place to check the accuracy of the testing instruments Kana was part of the Wits team that developed the SmartSpot technology which, in South Africa, has been used on all 289 GeneXpert testing instruments in the national TB programme since 2011

In 2020, Kana pivoted this technology to support national diagnosis of Covid-19 through supporting laboratories in the public sector He created a new series of products that enabled mass testing in South Africa, which have now been rolled out to 34 countries. For these and related activities, his team was awarded the South African NSTF-South32 Innovation Award: Corporate Organisation, for 2020/2021

Read how Wits University approaches innovation to advance society for good via the new Wits Innovation Centre (WIC)

Did you know the Wits Innovation Centre (WIC) lies at the heart of the University’s innovation ecosystem that seeks to develop an ‘innovation mindset’ across all disciplines and boundaries? Click the banner for info

Respiratory virus plagues SA but new vaccine for pregnant moms saves babies

Does immunising a woman during pregnancy protect her unborn baby against respiratory syncytial virus (RSV) in the months after it is born?This is what the MATISSE study conducted in 18 countries including South Africa aimed to find out.

The Maternal Immunization Study for Safety and Efficacy (MATISSE) phase 3 trial evaluated the efficacy and safety of maternal RSVpreF vaccination in preventing RSV-associated lower respiratory tract illness in infants

Respiratory syncytial virus [RSV] is the most common cause of hospitalisation in children under five years of age, and even more so in those younger than six months

Researchers at the Wits Vaccines and Infectious Diseases Analytics Research Unit (Wits VIDA) at the University of the Witwatersrand, Johannesburg, led the MATISSE trial in South Africa.

The researchers wanted to find out if administering Pfizer’s Bivalent Prefusion F Vaccine in pregnancy could reduce the burden of RSV-associated lower respiratory tract illness in new-borns and infants and, if so, how well, and for how long?

In this trial, as part of a multi-centred study, Wits VIDA report that vaccination of pregnant women with the RSV vaccine is safe, and reduces the risk of severe RSV associated lower respiratory tract infection by 82% in infants aged through to six months old

The findings were published in the New England Journal of Medicine (NEJM) on 5 April 2023.

The release of these study findings, in which South African scientists played a prominent role, comes at a time when RSV is back with a vengeance in SA, with paediatric wards being filled with children in whom illness can now be prevented with this new RSV vaccine.

says study author and Director of Wits VIDA, Professor Shabir Madhi.

gency to immunise against RSV espiratory tract infections (LRTI) are the most n cause of hospitalisation and death in children onths of age, particularly in low- and middlecountries (LMICs).

RSV is the most common cause of LRTI hospitalisation in children, occurring in some 30-80% of cases Approximately two-thirds of children will be infected at least once by RSV in the first two years of life, a third of whom will develop LRTI

In 2019, it was estimated that there were 101 400 RSV-attributable deaths, 99% of which occurred in LMICs and 50% of which were in children less than 6 months of age

Death from RSV is likely to be underestimated in lowincome settings. There has been no change in the burden of RSV over the past two decades.

RSV-LTRI immunisation a global priority and a LMIC urgency

Vaccines to prevent RSV-LRTI are considered a priority by the World Health Organization. There is currently no antiviral treatment for children with RSV infection, and management of RSV-LRTI is symptom based Palivizumab, a costly monoclonal antibody, is the only licensed effective strategy to reduce the risk of RSVLRTI hospitalisation in South Africa

The MATISSE study shows that the RSV prefusion F protein-based vaccine (RSVpreF) administered during the late second or third trimester of pregnancy may protect infants from severe RSV illness during the first few months of life – this would be particularly important in low- and middle-income countries, where the burden of RSV-associated lower respiratory tract illness is highest.

Wits and US Congress celebrate 20 years of PEPFAR

The Wits Reproductive Health and HIV Institute hosted a US Congress Delegation to mark the programme’s two decades of HIV/Aids relief.

The U.S. Congress delegation, led by Senator Lindsey Graham, Ambassador John Nkengasong, Ambassador Reuben Brigety and senior principals from the Elton John Foundation, visited the Wits Reproductive Health and HIV Institute based in the Hillbrow Health Precinct (HHP) in Johannesburg for a high-level science focused event They were given an opportunity to engage with world-class South African scientists and researchers to highlight key scientific activities and their impact on HIV programmes.

It was in 2003 that former President George W Bush initiated the U S President's Emergency Plan for AIDS Relief, known as PEPFAR Through PEPFAR, the U S government has invested over $100 billion in the global HIV/AIDS response, the largest commitment by any nation to address a single disease in history, saving 25 million lives, preventing millions of HIV infections, and accelerating progress toward controlling the global HIV/AIDS pandemic in more than 50 countries.

The Daily Maverick's J Brook Spector described it as "the most important public health/foreign assistance initiative ever undertaken, becoming a template for international efforts against other diseases."

What the world needs

Professor Helen Rees, Executive Director of Wits RHI, welcomed the delegation alongside Wits University's

Rees, an internationally recognised global health leader, established the Wits RHI in 1994 to support the new South African government and formulate and implement new national policies around sexual and reproductive health. It was in 2004 that the institute received its first grant from PEPFAR

She provided a brief overview of the history of Hillbrow and the HHP, providing a valuable context of the historical events that impact HIV research and programming in South Africa She also emphasised the need for partnerships, not just in South Africa but globally.

"What the world does not need, if we are worried about pandemics, is we do not need to neglect people who are immunocompromised in large numbers in any part of the world", adding that research has demonstrated that there are no borders

Rees told the delegation that there's a need to link the work done in collaboration with PEPFAR, with the global health community

"The PEPFAR program has come such a long way to helping us address HIV/AIDS but we're not there yet We need the preventative technologies that we're talking about, we need a vaccine, we need a cure but we're not there yet," she said

*Read full article

Vice-Chancellor and Principal Professor Zeblon Vilakazi and other key researchers from the institution

Successful cure of HIV infection after stem cell transplantation

An international group of researchers including Wits scientists have identified a third case of HIV infection cured by stem cell transplantation.

Haematopoietic stem cell transplantation for the treatment of severe blood cancers is the only medical intervention that previously cured two people living with HIV.

'Haematopoietic' refers to an immature cell that can develop into all types of blood cells, including white blood cells, red blood cells, and platelets Hematopoietic stem cells are found in the peripheral blood and the bone marrow and are also called blood stem cell

An international group of physicians and researchers, including Dr Annemarie Wensing of Ezintsha, a division of the Wits Health Consortium, and Dr Monique Nijhuis in the HIV Pathogenesis Research Unit at Wits, has now identified another case in which HIV infection has been shown to be cured in the same way

In a study published today in Nature Medicine, the successful healing process of this third patient was for the first time characterised in great detail virologically and immunologically over a 10-year duration

An infection with the human immunodeficiency virus (HIV) was previously considered incurable The reason for this is that the virus ‘sleeps’ in the genome of infected cells for long periods of time, making it invisible and inaccessible to both the immune system and antiviral drugs

The ‘Düsseldorf patient’, a 53-year-old man, is now the third person in the world to be completely cured of the HI virus by a stem cell transplant.

The patient, treated at the University Hospital Düsseldorf for his HIV infection, had received a stem cell transplant due to a blood cancer (leukaemia).

As in the cases of the first two patients, named ‘Berlin’ and ‘London’ respectively, the Düsseldorf patient received stem cells from a healthy donor whose genome contains a mutation in the gene for the HIV-1 co-receptor CCR5

This mutation makes it nearly impossible for most HI viruses to enter human CD4+ T-lymphocytes, their major target cells that cause HIV infection in humans Following transplantation, the Düsseldorf patient was carefully monitored virologically and immunologically for almost 10 years

Using a variety of sensitive techniques, the researchers analysed the patient’s blood and tissue samples to closely monitor immune responses to HIV and the continued presence or even replication of the virus

More than four years ago, the patient’s antiviral therapy against HIV was discontinued Ten years after transplantation and four years after the end of anti-HIV therapy, the Düsseldorf patient could be declared cured by the international research consortium.

We could not detect any complete HIV variants in tissues or blood. HIV immunity also faded away, which shows that the immune system is forgetting about the HIV infection that was once there This cure means that we do gain insight in the dynamics of the immune systems and the viral reservoirs during cure. The implications are that switching off the CCR5 receptor is a key step in these cures. However, the limitations are that stem cell transplantations cannot be performed on a large scale, so other ways to modify the receptor need to be studied.

says Clinical virologist Dr Annemarie Wensing

Wensing is an Honorary Professor at Ezintsha, a division of the Wits Health Consortium at Wits University in South Africa, and Assistant Professor at the University Medical Center Utrecht in the

Netherlands

Dr Monique Nijhuis, Honorary Professor in the HIV Pathogenesis Research Unit, School of Pathology at Wits University, and Associate Professor of Virology at the University Medical Center Utrecht in The Netherlands, was involved in the patients’ pathological analysis and was also a co-author of the 2023 Nature Medicine article

1 in 5 South African households begs for food –the link between food insecurity and mental health

At least ten million South Africans didn’t have enough food or money to buy food in 2019, according to the country’s statistics agency This food insecurity remains a leading health problem that is unlikely to be eradicated any time soon.

To support those affected, it’s important to understand how South African households cope with food insecurity Existing research on this has been conducted sub-nationally The focus has mostly been on the poorest regions of the country The national picture of household food insecurity has not been clear

Another gap in understanding has been the impact of households’ coping strategies on mental health Such strategies include eating less, borrowing or using credit, and even begging for food on the streets Our recent study investigated food insecurity and related coping strategies among South African households and their association with anxiety and depression.

We have shown, for the first time, how the strategies that South African households commonly use to cope with food insecurity are associated in different ways with anxiety and depression. In other words, some coping strategies may have a greater impact than others on mental health

Our findings suggest that begging for food was the most harmful coping strategy for mental health. Conversely, relying on less preferred and less expensive foods was less associated with anxiety and depression

The poor are the most food insecure

For this study, face-to-face interviews were conducted with a nationally representative sample of 3,402 adults in October 2021 The survey data was statistically weighted to represent over 39 million South African households

We assessed food insecurity using the Community Childhood Hunger Identification Project questionnaire This survey tool allowed us to categorise the households into three groups: food secure, at risk, and food insecure. The study found that over 20% (1 in 5) of the South African households were food insecure But the prevalence varied widely across the provinces The Eastern Cape province was the most affected (32% of households there were food insecure)

The study also confirmed that food access in South Africa largely depends on socio-economic status People who are uneducated, the unemployed and those receiving a low monthly income are the most severely affected by inadequate food access. Food insecurity was most common among coloured people (24%) – people of mixed European, African or Asian ancestry Black people (23%) were also more food insecure than white (5%) and Asian (4%) categories. These large differences in food insecurity rates have been attributed to former apartheid regime policies These policies led to racial discrimination, geographic segregation, and other unsustainable settlement patterns. Hence, solutions to such inequalities require fundamental restructuring of the South African economy

Many households beg for food?

Our findings demonstrated that living in a food insecure household was associated with a higher risk of anxiety and depression. One level increase in food insecurity (shifting from the “food secure” to the “at risk” or from the “at risk” to “food insecure”) was associated with being 1 7 times more likely to experience higher levels of anxiety or depression

Those who were using the strategy of begging for food were 2 3 times more likely to experience higher levels of anxiety and depression This confirms what has been recently suggested by several studies: that an increase in food insecurity and depressive symptoms during COVID-19 may be related

We used the Coping Strategies Index questionnaire to assess the extent to which South African households used harmful coping strategies when faced with food insecurity

All coping strategies were used to some extent. The most common strategy (used by at least 46%) was relying on less preferred and less expensive foods Sending household members to beg for food was the least common strategy. It was used by almost 21% (more than 1 in 5) of the households. Such a high rate of households begging for food was not expected Begging is a strategy often used by homeless people, and it’s sometimes seen as socially unacceptable Click here to see tabulated data on various coping strategies in response to the question, In the past two weeks, how often have you had to:

The impact on mental health

For example, the National Income Dynamics Study –Coronavirus Rapid Mobile Survey reported that the rise in food insecurity during COVID-19 lockdowns was accompanied by an increased rate of people screening positive for depressive symptoms

Finding solutions

To assess the risk of impaired mental health among the household respondents, the General Anxiety Disorder7 and Patient Health Questionnaire-9 questionnaires were used These are validated tools for screening symptoms of anxiety and depression, respectively

Overall, this study suggested that food insecurity in South Africa remains a major health problem And poorer households are disproportionately affected. Living in a food insecure household may be forcing poor South Africans to use a variety of coping strategies that ultimately lead to anxiety and depression

Our report is timely in light of the recent announcement by the South African government that it would prioritise the issues of unemployment, poverty and inequality In the 2022 State of the Nation Address the president stated that there would be several fundamental reforms primarily aimed at reviving economic growth This would ultimately assist in combating high employment and food insecurity rates.

*Read more on The Conversation

Qualitative Analysis Using Social Maps to Explore Young Women's Experiences With Social Support of their Oral PrEP Use in Kenya and South Africa

aimed to assess young women's uptake of and adherence to PrEP while developing scalable PrEP delivery strategies for African women in high HIV incidence settings A total of 2,550 AGYW (aged 16–25 years) enrolled in POWER between 2017 and 2020, at one of six clinics

Data collection

Wits researchers involved: Makhosazane Nomhle Ndimande-Khoza, Sinead Delany-Moretlwe Adolescent girls and young women (AGYW) are at disproportionate risk of HIV infection in subSaharan Africa, 79% of new infections among 10–19 year olds are in girls (UNAIDS, 2019). Preexposure prophylaxis (PrEP) is a highly effective HIV prevention method; yet, oral daily PrEP adherence is challenging for AGYW in sub-Saharan Africa, despite their desire to stay HIV-free.

Social barriers to AGYW PrEP uptake and use have been identified in previous HIV prevention studies, such as HIV- or sex-related stigma, low social support, or disapproval of using a female-controlled HIV prevention product from partners, family, peers, and healthcare workers Peer support and peer influence are important in terms of AGYW's sexual and reproductive health behaviour, as well as family support for AGYW's HIV

In this study, AGYW in South Africa and Kenya participated in a social mapping exercise as part of a focus group discussion (FGD), through which the nuance of various social influencer groups was explored This article explores AGYW's views on the impact of social influencers on their PrEP use and AGYW's perception of those influencers' PrEP knowledge and support during the study. An exercise with social network maps is used to identify the relative influence of various members of AGYW's social networks and explored the direction of that influence on PrEP use.

Methods

This analysis includes a subset of participants from two family planning clinics in Kisumu, Kenya, one adolescent-friendly clinic in Johannesburg, and a community mobile adolescent health clinic in Cape Town, South Africa Toward the end of the POWER accrual period, using convenience sampling, young women who attended any site activities or clinic visits were asked if they were willing to participate in an FGD To be eligible for the FGD, they had to have refilled at least one PrEP prescription since enrolling in the POWER study

Social Mapping Exercise

During the FGDs, participants were asked to complete a social mapping exercise They placed pre-labelled stickers of PrEP influencers on an egocentric circle map to indicate their strength of influence (i.e., from inner/most influential circle to outer/least influential circle Facilitators followed a semi-structured guide, which included questions about participants' sticker choices placed accordingly

Conclusion

Using an ego-centric social network mapping tool to explore the relative influence of multiple influencers at once, AGYW described key supporters and detractors of their PrEP use, such as mothers, clinic counsellors, sex partners, and best friends

Successful approaches to supporting PrEP use should include youth-friendly services and counselling, interventions to increase community awareness about PrEP, which would facilitate support from mothers and best friends, address partner concerns about PrEP, and reduce stigma. Such interventions could foster effective PrEP use among adolescents to maximize the public health impact and reduce AGYW HIV infections *Read the full study

Intimate Partner Violence and Engagement in the HIV Care Continuum among Women in Sub-Saharan Africa: A Prospective Cohort Study

Wits researchers involved: This study is a collaboration of researchers of Wits Vida, Wits RHI, NICD

COVID-19 vaccine rollout is lagging in Africa, where there has been a high rate of SARS-CoV-2 infection This study aimed to evaluate the effect of SARS-CoV-2 infection before vaccination with the ChAdOx-nCoV19 (AZD1222) vaccine on antibody responses through to 180 days.

Methods

This study unmasked post-hoc immunogenicity analysis after the first and second doses of AZD1222 in a randomised, placebo-controlled, phase 1b-2a study done in seven locations in South Africa AZD1222 recipients who were HIV-uninfected were stratified into baseline seropositive or seronegative groups using the serum anti-nucleocapsid (anti-N) immunoglobulin G (IgG) electroluminescence immunoassay to establish SARS-CoV-2 infection before the first dose of AZD1222

Binding IgG to spike (anti-S) and receptor binding domain (anti-RBD) were measured before the first dose (day 0), second dose (day 28), day 42, and day 180 Neutralising antibody (NAb) against SARS-CoV2 variants D614G, beta, delta, gamma, and A VOI V2, and omicron BA1 and BA 4 variants, were measured by pseudovirus assay (day 28, day 42, and day 180). This trial is registered with ClinicalTrials gov, NCT04444674, and the Pan African Clinical Trials Registry, PACTR202006922165132

Findings

Of 185 individuals who were randomly assigned to AZD1222, 91 individuals who were baseline seropositive were included and 58 were baseline seronegative, in the final analysis. In the seropositive group, there was little change of anti-S IgG (and antiRBD IgG) or neutralising antibody (NAb) titres at day 42 compared with day 28 Anti-S (and anti-RBD) IgG geometric mean concentrations (GMCs) were higher throughout in the seropositive compared with the seronegative group, including at day 180 (GMCs 517 8 [95% CI 411 3-651 9] vs 82 1 [55 2-122 3] BAU/mL)

Also, D614G NAb geometric mean titres (GMTs) were higher in the seropositive group than the seronegative group, as was the percentage with titres of at least 185 (80% putative risk reduction threshold [PRRT] against wild-type-alpha COVID-19), including at day 180 (92 0% [74 0-99 0] vs 18 2% [2 3-51 8). Similar findings were observed for beta, A VOI V2, and gamma For delta, BA 1, and BA 4, NAb GMTs and the proportion with titres above the PRRT were substantially higher in the seropositive compared with seronegative group at day 28 and day 42, but no longer differed between the groups by day 180

Interpretation

A single dose of AZD1222 in the general African population, where COVID-19 vaccine coverage is low and SARS-CoV-2 seropositivity is 90%, could enhance the magnitude and quality of antibody responses to SARS-CoV-2 *Read the full study

Extension of

Composite Quality

of metaepidemiological evidence

Wits researchers involved: Steffen Mickenautsch

To survey current meta-epidemiological studies to identify additional trial design characteristics that may be associated with significant over- or underestimation of the treatment effect and to use such identified characteristics as a basis for the formulation of new CQS appraisal criteria.

Materials and methods

A retrieval of eligible studies was made from two systematic reviews on this topic (latest search May 2015) and searched the databases PubMed and Embase for further studies from June 2015 –March 2022 All data were extracted by one author and verified by another Sufficiently homogeneous estimates from single studies were pooled using random-effects meta-analysis Trial design characteristics associated with statistically significant estimates from single datasets (which could not be pooled) and meta-analyses were used as a basis to formulate new or amend existing CQS criteria

Results

A total of 38 meta-epidemiological studies were identified From these, seven trial design characteristics associated with statistically significant over- or underestimation of the true therapeutic effect were found.

Conclusion

One new criterion concerning double-blinding was added to the CQS, and the original criteria for concealing the random allocation sequence and for minimum sample size were amended

*Read the full study

The Value of Explicit, Deliberative, and Context-Specified Ethics Analysis for Health Technology

Assessment: Evidence from a Novel Approach Piloted in South Africa

Wits researchers involved (PRICELESS SA): Aviva Tugendhaft, Susan Goldstein, Atiya Mosam, Karen Hofman

This article explores the perceived value, including associated strengths and challenges, of using a context-specified ethics framework to guide deliberative health technology appraisals.

Methods

The South African Values and Ethics for Universal Health Coverage (SAVE-UHC) approach, piloted in South Africa, consisted of 2 phases: (1) convening a national multistakeholder working group to develop a provisional ethics framework and (2) testing the provisional ethics framework through simulated health technology assessment appraisal committee meetings (SACs) Three SACs each reviewed 2 case studies of sample health interventions using the framework Participants completed postappraisal questionnaires and engaged in focus group discussions

Results

The SACs involved 27 participants across 3 provinces Findings from the postappraisal questionnaires demonstrated general support for the SAVE-UHC approach and content of the framework, high levels of satisfaction with the recommendations produced, and general sentiment that participants were able to actively contribute to appraisals.

Conclusion

This work highlights how the combination of a contextspecified ethics framework and structured deliberative appraisals can contribute to the quality of health technology appraisals and transparency of health priority setting *Read the full study

the

Score (CQS) as an appraisal tool for prospective, controlled clinical therapy trials-A systematic review

Active travel and paratransit use in African cities: Mixed-method systematic review and meta-ethnography

Wits researchers involved: Lee Randall, Lisa Jayne Ware, Lisa Micklesfield, Gudani Mukoma, Sostina

Spiwe Matina

Active travel, as a key form of physical activity, can help offset noncommunicable diseases as rapidly urbanising countries undergo epidemiological transition. In Africa, a human mobility transition is underway as cities sprawl and motorization rise and preserving active travel modes (walking, cycling and public transport) is important for public health. Across the continent, public transport is dominated by paratransit, privately owned informal modes serving the general public.

Methods

This study reviewed the literature on active travel and paratransit in African cities, published from January 2008 to January 2019 It included 19 quantitative, 14 mixed-method and 8 qualitative studies (n = 41), narratively synthesizing the quantitative data and metaethnographically analysing the qualitative data

Findings

Integrated findings showed that walking was high, cycling was low and paratransit was a critical mobility option for poor peripheral residents facing long livelihood-generation journeys As an indigenous solution to dysfunctional mobility systems shaped by

colonial and apartheid legacies it was an effective connector, penetrating areas unserved by formal public transport and helping break cycles of poverty

From a public health perspective, it preserved active travel by reducing mode-shifting to private vehicles Yet many city authorities viewed it as rogue, out of keeping with the ‘ideal modern city’, adopting official anti-paratransit stances without necessarily considering the contribution of active travel to public health

Interpretation

The studies varied in quality and showed uneven geographic representation, with data from Central and Northern Africa especially sparse; notably, there was a high prevalence of non-local authors and out-ofcountry funding Nevertheless, drawing together a rich cross-disciplinary set of studies spanning over a decade, the review expands the literature at the intersection of transport and health with its novel focus on paratransit as a key active travel mode in African cities Further innovative research could improve paratransit's legibility for policymakers and practitioners, fostering its inclusion in integrated transport plans

*Read the full study

Global investments in pandemic preparedness and COVID-19: Development assistance and domestic spending on health between 1990 and 2026

response, and pandemic preparedness and response using a keyword search were used for this study Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need

Findings

Wits researchers involved: Micheal Boachie

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. This study aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in

pandemic preparedness

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, four sources of health spending were estimated, namely: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. To estimate spending, the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) were used An estimated development assistance for general health, COVID-19

In 2019, at the onset of the COVID-19 pandemic, US$9 2 trillion (95% uncertainty interval [UI] 9 1-9 3) was spent on health worldwide This study found great disparities in the number of resources devoted to health, with high-income countries spending $7 3 trillion (95% UI 7 2-7 4) in 2019; 293 7 times the $24 8 billion (95% UI 24 3-25 3) spent by low-income countries in 2019 That same year, $43·1 billion in development assistance was provided to maintain or improve health.

The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1 8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37 8 billion was provided for the health-related COVID-19 response Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252 2% of the recommended target Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021 This study poses a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

*Read the full study

The Value of Explicit, Deliberative, and Context-Specified Ethics Analysis for Health Technology Assessment: Evidence from a Novel Approach Piloted in South Africa

Wits researchers involved (PRICELESS SA): Aviva Tugendhaft, Susan Goldstein, Atiya Mosam, Karen Hofman

This article explores the perceived value, including associated strengths and challenges, of using a context-specified ethics framework to guide deliberative health technology appraisals

Methods

The South African Values and Ethics for Universal Health Coverage (SAVE-UHC) approach, piloted in South Africa, consisted of 2 phases: (1) convening a national multistakeholder working group to develop a provisional ethics framework and (2) testing the provisional ethics framework through simulated health technology assessment appraisal committee meetings (SACs). Three SACs each reviewed 2 case studies of sample health interventions using the framework Participants completed post-appraisal questionnaires and engaged in focus group discussions.

Results

The SACs involved 27 participants across 3 provinces Findings from the post-appraisal questionnaires demonstrated general support for the SAVE-UHC

approach and content of the framework, high levels of satisfaction with the recommendations produced, and general sentiment that participants were able to actively contribute to appraisals Qualitative data showed participants perceived using a contextspecified ethics framework in deliberative decisionmaking: (1) supported wider consideration of and deliberation about morally relevant features of the health coverage decisions, thereby contributing to the quality of appraisals; (2) could improve transparency; and (3) offered benefits to those directly involved in the priority-setting process Participants also identified some challenges and concerns associated with the approach

Conclusion

The SAVE-UHC approach presents a novel way to develop and pilot a locally contextualized, explicit ethics framework for health priority setting This work highlights how the combination of a context-specified ethics framework and structured deliberative appraisals can contribute to the quality of health technology appraisals and transparency of health priority setting

*Read the full study

Indirect Effects of COVID-19 on maternal and child health in South Africa

quintiles, geographical areas and provinces To account for confounding by underlying seasonal or linear trends, a segmented fixed effect panel model was subsequently fitted

Results

Wits researchers involved: This study is a collaboration of researchers of PRICELESS SA and Wits Agincourt

The unfinished burden of poor maternal and child health contributes to the quadruple burden of disease in South Africa with the direct and indirect effects of the COVID-19 pandemic yet to be fully documented To investigate the indirect effects of COVID-19 on maternal and child health in different geographical regions and relative wealth quintiles.

Methods

This study estimated the effects of COVID-19 on maternal and child health from April 2020 to June 2021 These estimates were made by calculating mean changes across facilities, relative wealth index (RWI)

A total of 4956 public sector facilities were included in the analysis. Between April and September 2020, full immunisation and first dose of measles declined by 6 99% and 2 44%, respectively In the follow-up months, measles first dose increased by 4 88% while full immunisation remained negative ( 0 65%), especially in poorer quintiles. At the facility level, the mean change in incidence and mortality due to pneumonia, diarrhoea and severe acute malnutrition was negative Change in first antenatal visits, delivery by 15–19-year olds, delivery by C-section and maternal mortality was positive but not significant.

Conclusion

COVID-19 disrupted the utilisation of child health services While the reduction in child health services at the start of the pandemic was followed by an increase in subsequent months, the recovery was not uniform across different quintiles and geographical areas This study highlights the disproportionate impact of the pandemic and the need for targeted interventions to improve utilisation of health services

*Read the full study

MRI findings of children with suspected hypoxic-ischaemic injury at a Tertiary Academic Hospital in Johannesburg, South Africa

Hypoxic ischaemic injury (HII) is characterized by altered cerebral blood flow and decreased oxygenation resulting in neurologic dysfunction. Clinical manifestations of hypoxic ischaemic injury range from neonatal encephalopathy to seizure disorders and cerebral palsy in older children. HII and its clinical sequelae present a global health burden with significant morbidity and mortality in neonates, infants and older children Magnetic resonance imaging (MRI) is recognized as the gold standard in identifying the aetiology of neonatal encephalopathy, identifying patterns of HII and a diagnostic tool for predicting long-term neurologic outcomes

Materials and Methods

Hypoxic ischaemic brain injury and its clinical sequalae

Wits researchers involved: Liam Lorentz, Nasreen Mahomed, Tanyia Pillay

Cont

present a global health burden MRI is the imaging modality of choice to investigate hypoxic-ischaemic injury As there is limited data from low and middleincome countries describing MRI findings of children with suspected hypoxic-ischaemic brain injury, this research describes the MRI findings of children with suspected hypoxic-ischaemic brain injury in a resource-limited setting

Results

A total of 128 MRI studies were evaluated MRI evidence of hypoxic-ischaemic injury was found in 42 2% of children Normal MRI findings were present in 41 (32 0%) children; and punctate periventricular

white matter injuries in 19 5%, watershed injury in 3 1%, central injury in 10 2% and diffuse injury in 23.4% of MRI studies. Preterm infants more commonly demonstrated periventricular white matter injury

Conclusion

Periventricular white matter pattern of injury was the most common type in premature infants, congruent with international cohorts Despite the majority of children with suspected hypoxic-ischaemic injury being imaged beyond the infant period, MRI findings may have implications for medicolegal recourse.

*Read the full study

Compliance of medical practitioners with diabetic treatment guidelines in West Rand, Gauteng

This study was conducted in the outpatient department of Dr Yusuf Dadoo Hospital in West Rand, Gauteng. A total of 323 records of patients seen from August 2019 to December 2019 were reviewed, and some of the basic variables were assessed according to the most recent diabetic treatment guidelines SEMDSA 2017.

Results

Wits researchers involved: Nneka Ohanson, Deidré Pretorius

Diabetes mellitus is increasing globally and is associated with multiple complications. Guidelines have been formulated to standardise care among people living with diabetes mellitus (DM), but research shows poor compliance with treatment guidelines. This study aimed to assess how well healthcare practitioners in a district hospital in Gauteng complied with the most recent diabetic treatment guideline, Society for Endocrinology Metabolism and Diabetes South Africa (SEMDSA) 2017.

Methods

A retrospective cross-sectional review of patient records living with diabetes was done

Files were audited in four categories: comorbidities, examinations, investigations and the presence of complications Six monthly glycated haemoglobin (HbA1c) was assessed in 40 (12 4%), annual creatinine assessed in 179 (55.4%) and lipogram in 154 (47.7%) of patients More than 70% of patients had uncontrolled glycaemia and two people were screened for erectile dysfunction

Conclusion and Contribution

Monitoring and control parameters were infrequently done as per guideline recommendations The resultant effects were poor glycaemic control and thus numerous complications

Targeted strategies to improve medical practitioner compliance to guidelines including further research to study factors associated with poor compliance with guidelines are needed to improve the overall care of people living with DM in the West Rand and thus minimise the risk of complications among patients in the district

*Read the full study

Wits’ young human genetics scientists excel at the YIF2023

In February 2023, researchers and scientists from the Wits Division of Human Genetics attended the Young Investigators Forum The young scientists from the Division of Human Genetics presented their research projects. A summary on each of the presentations is provided below

Dr David Twesigomwe was awarded the Best oral presentation

the Wits-H3Africa/GSK ADME collaboration. The talk also highlighted the utility of StellarPGx, a novel pharmacogenomics analysis pipeline developed at the SBIMB

The findings of this research underscore the need for investigating pharmacogene variation in the African context to reliably inform clinical pharmacogenomics implementation in Africa This will in turn contribute to mitigating the risk of adverse drug reactions and promoting treatment efficacy in clinical settings

*Read the full study

Prenatal Genetic Counselling Services in Johannesburg

Dr Twesigomwe, a postdoctoral fellow at the Sydney Brenner Institute for Molecular Bioscience (SBIMB) presented his PhD research titled “Characterisation of pharmacogene haplotype variation in African populations"

His research set out to characterize the variation in genes that encode key drug-metabolizing enzymes (such as CYP2D6) across African populations, which have been vastly underrepresented in pharmacogenomics to date

At the conference, Dr Twesigomwe’s talk highlighted frequencies of known star alleles (haplotypes) in CYP2D6, CYP2B6, and CYP2A6, as well as information on novel African-ancestry star alleles identified under

Elzette Nienaber, Wits lecturer and registered Genetic Counsellor at (NHLS) presented a poster at the conference for her research work titled Elzette Nienaber “Prenatal genetic counselling services in a Johannesburg healthcare setting: An overview”.

This study aimed to evaluate and assess the prenatal genetic service provided by genetic counsellors from the Division of Human Genetics at the NHLS/Wits

Genetic counselling clinic records were retrospectively analysed from July 2019 to June 2022 to examine the reason for referral, ultrasound screening outcome and uptake of invasive testing

The findings of this study emphasize the value of prenatal genetic counselling services and highlight areas to address which can improve the overall service

Pharmacogenetic Variation in Sub-Saharan Africa

Blessing Rotondwa Sitabule, a PhD candidate in the School of Pathology presented a poster titled “Structural Bioinformatics Analysis of CYP2D6 Pharmacogenetic Variation Relevant to Sub-Saharan African Populations”

The project focused on assessing the potential impact of missense variants on the CYP2D6 enzyme using structural bioinformatics methods such as molecular dynamics and Structural Workflow for Annotating ADME gene Targets (SWAAT) The research showed how variants such as T107I (forms part of the *17 allele which is prevalent in Africa) and V338M (forms part of the *29 allele which is prevalent in Africa) influence the stability and mobility of the enzyme These may have implications for the efficiency of the enzyme which may explain the differences in drug response as a result of genetic variation.

Paediatric Liver Transplants

Caitlin Wheeler presented her MSc research titled “Impact of donor CYP3A5 genotype on pharmacokinetics of tacrolimus in South African paediatric liver transplant patients” as a poster and a speed talk at the conference

Her study focused on the optimal therapeutic drug levels of tacrolimus, and immunosuppressants being critical for preventing solid organ rejection, especially in paediatric liver transplant recipients Pharmacogenetic research suggests that SNPs within CYP3A5 contribute towards the specific inter-patient tacrolimus dosing requirements observed in transplant clinics This study aimed to compare the pharmacokinetics of tacrolimus for paediatric liver transplant patients to the donors’ CYP3A5 genotypes in a South African context considering donor and recipient characteristics.

Bill and Melinda Gates Foundation Rising Star

Session

Earlier this month, Wits RHI’s young researchers had the privilege of attending the first Rising Stars session hosted Bill and Melinda Gates Foundation (BMGF) to help early- and mid-career researchers gain vital insight into networking, career progression, and accessing funding. The theme for the evening was, Creating Connections, Building Bridges.

The session hosted experienced researchers such as Prof Bavesh Kana, Prof Mosa Moshabela, and Dr Nina Russell to talk about their careers, mentors, and the thematic lessons they learned through their experiences These inspirational stories inspired the young researchers, and there were many valuable lessons to be learnt Representatives from BMGF and

SA MRC gave insight into the opportunities for young researchers to access research funding and grants

The researchers had the opportunity to practice the networking skills that they had picked up from the talks and this was the foundation for virtual networking where young researchers could connect across the country

A group of Wits RHI’s rising stars was extremely grateful to have had the opportunity to participate in this event. The young rising stars from Wits RHI were:

• Glory Chidumwa

• Roisin Elizabeth Drysdale

• Lisa Mills

• Mpho Moji

• Jean le Roux

Professor Ivor Douglas on co-edits a textbook on critical care

Congratulations to Professor Ivor Douglas (MBBCh, 1990) who co-edited the fifth edition of the textbook “Principles of critical care“.

Professor Douglas is an esteemed published researcher and critical care expert

He says as textbook sceptics, him and his co-authors

have endeavoured to revise and update the core text as a highly readable, accessible and usable reference for critical care specialists, and affiliated disciplines

Dr Stefan Grant on appointed as

Section Chief of Hematology and Medical

Oncology

The Wits Faculty of Health Sciences congratulates Dr Stefan Grant (MBBCh, 1981) on his appointment as the Section Chief of Hematology and Medical Oncology of Tulane University School of Medicine as well as Deputy Director of the Tulane Cancer Center and as Deputy Director

of the Louisiana Cancer Research Center

Dr Grant is a thoracic medical oncologist and a published researcher with an interest in pulmonology, respiratory medicine, clinical trials, and immunologic approaches to the treatment of lung cancer

Dr Grant is also a registered patent attorney and holds an MBA He continues to serve in numerous leadership roles in clinical medicine as well as the realm of Intellectual Property.

Professor Helen Rees conferred with a degree of Doctor of Laws (LLD) by Rhodes University

OUTSTANDING ACHIEVEMENTS Prof Bavesh Kana awarded a gold medal for tuberculosis molecular diagnosis

It's World TB Day and award-winning microbiologist Bavesh Kana knows molecular diagnostics can take on this lethal bacterial disease that still kills millions

The World Health Organization (WHO) recognises 24 March as World TB Day, the theme of which this year is Yes! We can end TB!

The theme aims to inspire hope and encourage highlevel leadership, increased investments, faster uptake of new WHO recommendations, adoption of innovations, accelerated action, and multisectoral collaboration to combat the TB epidemic

Stepping up on the high-level leadership and adoption of innovations front is Wits Professor Bavesh Kana who directs the Wits node of the Centre of Excellence for Biomedical TB Research (CBTBR)

Earlier this month Kana was awarded a Gold Medal at the 9th Scientific Merit Awards hosted by the South African Medical Research Council (SAMRC)

These awards are among South Africa’s most prestigious and are dedicated to contributions to health research in South Africa

Gold medals are awarded to established senior scientists who have made seminal scientific contributions that have impacted people’s health, especially that of those living in developing countries

Innovation in molecular diagnostics

Molecular diagnostics are laboratory methods that are used to help identify a disease – or the risk of developing a disease – by sequencing a patient’s DNA or RNA for markers of potential diseases in future.

Kana’s research focuses on TB diagnostics, vaccines and the discovery of new TB drug targets More recently, he has directed efforts towards developing new molecular diagnostics for a range of diseases.

*Read more

Watch the video

OPPORTUNITIES

CREATING OPPORTUNITIES FOR CURRENT STUDENTS

Your experience, networking, mentoring, and workplace skills could assist facilitate professional development sessions for students

The Office of Student Success (OSS) at the Wits Health Sciences Faculty, invites alumni to participate in the Umsebenzi journey with Health Science students towards employability

More specifically, Umsebenzi aims to:

To encourage students to develop and transfer their current skills into future professional environments Promote the smooth transition of graduates into the workplace Equip students with job search skills. Share existing prospective employment opportunities

THE HUMAN GUT MICROBIOME MAPPING PROJECT

Have you heard of the gut microbiome?

In a nutshell, the microbiome is a collection of microbes (bacteria, viruses, fungi etc) and their genes, that are both helpful and possibly harmful, which naturally live on and inside of your body Everyone has a unique system of gut microbiota that is originally established at birth An individual’s gut microbiome profile is either positively affected (beneficial to health) or negatively affected (increase risk for disease) by changes to their environment, diet, lifestyle and even socioeconomic status

The study is open to all Wits staff and students as well as their family and household members above the age of 18 years For any queries, please email cmmi@csir co za

PARTICIPATE IN THE METHYLPHENIDATE STUDY TO MEASURE THE EFFECTS ON PHYSICAL AND COGNITIVE PERFORMANCE

Adults and children from 8-year-olds are invited to participate in a study being undertaken at Wits Univeristy to measure the effects on physical and cognitive performance (e g attention)

For more information or to participate please contact: Prof D Constantinou 011 717 3396 / 011 717 3372

Sign-up

Sign-up

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JUNE 26

Faculty of Health Sciences Masters & PhD Writing Retreat

As part of our effort to support students who are at the stage of writing up their research reports, dissertations or theses, the Health Sciences Research Office will be running a 4-day writing retreat for postgraduate students registered in the Faculty of Health Sciences, University of the Witwatersrand

During the retreat, candidates will focus exclusively on writing Experienced facilitators will be available to guide and review write-ups produced by the participants

Additional support such as scientific writing skills, referencing, database searching, statistical and qualitative assistance will be arranged as per your needs during the retreat. Kindly note: There are only 20 spaces available so it will be on a first-come, first-serve basis

Time: 8h30 - 16h30 (tea/coffee and lunch will be provided)

Venue: Phillip V Tobias Health Sciences Building (Exact details will be given to the selected candidates)

28th Biennial Surgical Symposium on the 26th and 27th June 2023

The programme includes two workshops: A Journey Through a MMED Research Project that will help you gain valuable insight into everything you need to know about doing your MMed research; and a Hernia Workshop, a 2-day complimentary course for Senior registrars and Consultants

Using only examples relevant to surgical research, this 1-day course will cover all aspects of the MMed research process, from choosing a topic, writing a literature review, getting ethics/institutional approval, capturing your data, basic statistical data analysis, writing your final report, to authorship & publication

Guest speakers: Dr Rebecca M Minter, a A R Curreri Professor and Chair: Department of Surgery University of Wisconsin School of Medicine and Public Health