Researchers have identified a mechanistic link between zinc levels in humans and the risk of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The research, published today as a Reviewed Preprint in eLife, is described by editors as a fundamental study that substantially advances our understanding of the role of zinc in metabolism. The evidence comes from genetic analysis of a large population of human participants and comprehensive lab studies of a potential therapeutic target for NAFLD and type 2 diabetes.
Converging lines of evidence have shown that zinc plays a crucial role in insulin production and glucose metabolism. “We know that increasing zinc intake improves blood glucose control in people with prediabetes or type 2 diabetes, and people with a mutation in a key zinc transporter protein have reduced risk of diabetes.” says first author Shek Man Chim, Principal Scientist at Regeneron Pharmaceuticals, Inc, New York, US. “However, the mechanism for how zinc influences systemic blood glucose levels and diabetes risk remains unclear.”
To explore the diabetes-protective role of zinc, Chim and colleagues tested loss-of-function mutations from genetic sequence data collected from a large population of participants of European ancestry who took part in the Regeneron Genetics Center-Geisinger Health System DiscovEHR study. This identified a rare mutation that causes loss of function in a zinc transporter protein called SLC39A5, associated with increased circulating zinc levels.
To confirm this, they looked at how loss-of-function mutations in SLC39A5 were associated with type 2 diabetes in a meta-analysis of four multi-ethnic European and US studies totalling >62 000 cases of diabetes and > 518 000 healthy controls. This confirmed that circulating zinc levels in carriers of the SLC39A5 loss-of-function mutation were elevated and associated with a reduced risk of diabetes.
Having identified SLC39A5 as an important clinical link between zinc and diabetes, the team explored its function by genetically deleting the zinc transporter protein in mice. As anticipated, these mice had elevated blood and tissue levels of zinc. When the team fed mice a high-fat, high-fructose diet to induce obesity, there was a significant reduction in fasting glucose compared to the control mice fed the same diet. Similar results were observed in a congenital (leptin receptor-deficiency) model of obesity. Loss of SLC39A5 also resulted in reduced insulin resistance.
As diabetes often coincides with NAFLD, the team explored whether loss of SLC39A5 protects the liver, too. As hoped, mice lacking SLC39A5 had less build-up of fat in the liver and in blood markers of liver damage. Moreover, mice lacking SLC39A5 but fed a high-fat, high-fructose diet also had less fat accumulation in the liver and improved insulin sensitivity compared to control mice.
The improvements seen in the livers of mice lacking SLC39A5 prompted the researchers to see whether loss of SLC39A5 protects against progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis (NASH), a more severe liver inflammation that leads to fibrosis. They used a high-fat, high-cholesterol diet to induce NASH in mice and found increased markers of liver damage, body weight, fasting blood glucose and liver fibrosis. By contrast, the mice lacking SLC39A5 had reduced liver damage markers, fasting blood glucose and improvements in liver inflammation and fibrosis.
One concern highlighted by public reviewers was that observed differences in the metabolic consequences of SLC39A5 inactivation between male and female mice remained unclear. Further work will need to explore this further, as well as characterise the role of SLC39A5 in pancreatic cell function and glucose tolerance more fully.
“Our study provides for the first-time genetic evidence demonstrating the protective role of zinc against high blood sugar and unravels the mechanistic basis underlying this effect,” concludes senior author Harikiran Nistala, currently Head of functional Genomics at Alkermes Inc, Waltham, US. “Our observations suggest that blocking SLC39A5 could be a potential therapeutic avenue for type 2 diabetes and other indications where zinc supplementation alone is inadequate.”
The Law Society of South Africa (LSSA) has urged members of the public and civic associations to formally object to proposed amendments to the Road Accident Fund Act which, if approved, will have “dire consequences” for all South African road users.
The draft amendment bill was gazetted earlier this month by the transport minister. It proposes major changes to how the fund operates and how it will pay claims.
According to the LSSA, it proposes significant changes to the existing law, including removing the rights of drivers, passengers and pedestrians to claim compensation for injuries they have suffered. Instead, it proposes that the fund will only provide significantly reduced “social benefits”.
And, says the LSSA, an innocent injured party would still be denied the common law claim against the guilty party for the balance of his or her loss.
Yet all road users contribute directly or indirectly to the fund through the fuel levy, estimated to be about R45-billion a year.
“The poor and disempowered, who make up the vast majority of claimants and who are compelled to use public transport, will bear the brunt of the consequences of these amendments. They will be forced into the public health system, as the prescribed tariffs will not cover the actual costs incurred at a private hospital. Under the present system, many receive treatment at dedicated private healthcare facilities,” the LSSA says in its statement.
Claimants will also not receive any lump sum payments and, if they are not able to produce a payslip, it was unlikely that they would receive compensation for loss of earnings.
The LSSA said those who can afford it will be compelled to take out private accident cover for medical and other expenses as well as accident benefits.
“This is likely to be very costly, as there will be no reimbursement of expenses covered from the fund. Medical aids will more than likely exclude cover or the cost thereof will have to materially increase to preserve the funds in the pool for all members.”
The LSSA said road accident victims will be uniquely discriminated against by the proposed legislation.
“Their rights to be compensated for harm suffered by the fault of another will be taken away. Persons who suffer harm from medical negligence or are injured in train or plane or boat accidents or in shopping centres, hotels, construction sites, holiday resorts, private homes or by electrocution or pollution and by a host of other causes, have unfettered rights to seek compensation from the person or entity who caused them harm.
“Innocent motor vehicle accident victims, alone, do not have this right, despite the fact that they pay premiums to the fund.”
At present, injuries sustained in a motor car accident anywhere in South Africa by any person are covered by the Fund.
The Bill now excludes injuries suffered in motor vehicle accidents in parking areas, sports fields, farm roads, driveways, private estates, game reserves or any other private road.
People who are not citizens or permanent residents are also not covered.
Persons crossing a highway are not covered. Persons injured in a hit and run are not covered. Pedestrians, drivers and cyclist who may test over the legal limit for alcohol and their dependents are not covered.
The Bill also proposes doing away with payments for pain and suffering, loss of amenities of life, disability, disfigurement or shock.
It also does away with lump sum payments for loss of earnings or support, replacing them with monthly payments, and giving the fund the right to continually reassess its liability to continue to pay.
While at present all medical and other expenses reasonably incurred that arise directly from the accident are covered, these will now be subject to a prescribed tariff. Any future medical expenses have to be pre-authorised.
The LSSA said the Bill also largely ousts the role of the courts in determining contested claims, establishing instead alternative dispute resolution procedures followed by referral to be a yet-to-be established Road Accident Fund Adjudicator.
Co-chair of the KZN Personal Injury Lawyers Association Anthony De Sousa said the biggest issues around the Bill was what was not known, such as what “social benefits” were and what the treatment tariffs would be.
“We don’t know what we are signing up for”.
“What also worries me is the people it excludes, such as pedestrians crossing highways. They don’t do that for fun. They do it because they have no choice and are trying to get to work or home.
“They are poor people and if they are knocked down, they really need help. To exclude them is just weird.”
He said while there may be a case not to cover motorists who don’t have licences, or who are over the legal alcohol limit, the Bill also proposed that their dependents are not covered, such as a child who is injured.
“The kids are not at fault, but suddenly they have no claim.”
He said the approach seemed to be: “Let’s try and save some money”.
“We pay a lot of money to the fund in terms of the levy. If you were to take that money and take up an insurance policy, you would probably get better cover and better value for money.
“I don’t think, no matter how they change it, it won’t work until they sort out the dysfunctionality, the administrative inefficiencies in the fund. You can change it to whatever system. They cannot properly administer it and run it.
“If they did their jobs properly, the fund would be saving itself a bucket load of money.”
De Sousa said the association was presently putting together its formal response to the proposals.
Collen Msibi, spokesperson for the Department of Transport said, “The bill is out for comments. The department will welcome all views and suggestions for its consideration.”
As of the 1st of September 2023, the Hospice Palliative Care Association (HPCA) is known as the Association of Palliative Care Centres (APCC).
“This rebranding is not just a visual change,” says Ewa Skowronska, CEO of the APCC. “It is an important message to all medical professionals and the public that our members (many of whom still refer to themselves as hospices) offer quality, specialised and expert palliative care services. Too many people equate hospice with end-of-life only and many medical professionals refer very late. This leads to thousands of patients, and their loved ones, missing out on the holistic support that palliative care provides – support that, ideally, should be from diagnosis of a life-threatening illness and not solely in the last few days of life.”
The rebrand includes a new logo element that reflects that palliative care can be provided alongside curative treatments and into end-of-life care, including bereavement support (if needed).
“Our members adhere to the Standards for Palliative Healthcare Services, 4th edition, 2020 approved by the Council for Health Service Accreditation of South Africa (COHSASA) and the International Society for Quality in Health Care (ISQua),” says Leigh Meinert, Advocacy and Operations Manager of APCC. “This is important as sometimes there is a perception that our members are only servicing patients who do not have private healthcare support and might not be at the same level as private organisations. In reality, they have decades of palliative care experience, and compliance with these Standards ensures an ongoing level of excellence.”
As much as 90% of APCC member’s services are provided to the patient in the comfort of their own home. The patient’s loved ones are also supported by way of an interdisciplinary team. Such a team typically consists of a medical doctor, nurse, social worker, and home-based carers who can work alongside the patient’s healthcare professional and support quality of life.
Palliative care covers conditions such as HIV/AIDS, drug-resistant TB, chronic respiratory diseases, cardiovascular and neuromuscular diseases, MND and more. “Both adults and children are catered for,” says Meinert. “While patients can move in and out of a palliative care service, they may remain beneficiaries of the services for as long as they (or their loved ones) need or wish to. Patients may be discharged from the service if they are doing well and able to function independently. This is always negotiated between the patient, family, and members of the care team. We encourage patients to engage with an APCC member from the point of diagnosis as this helps to dispel fears and provides insight into the holistic services that can be offered. We believe that all patients have benefitted from an improved quality of life through the supportive care received from APCC members.”
“APCC has a cloud-based patient care monitoring, evaluation and reporting system able to report in detail on interventions given to any patient,” says Skowronska. “Our members are comfortable working alongside the primary clinician or specialist. They can provide a supportive extension of care to the patient and their loved ones and, in most cases, the APCC members inter-disciplinary teams collaborate and work alongside the referring doctors who are treating the patient. They also provide supportive care to the patient’s loved ones. This may include advanced healthcare planning, as well as psychosocial and spiritual support.”
“Our palliative care definition says it all,” concludes Meinert. “Palliative care is the physical, psychological, social and spiritual care provided by an interdisciplinary team of experts to anyone with a life-threatening illness and their loved ones. Care is offered from the point of diagnosis and extends to bereavement support if needed. Over 90% of the care that APCC members provide is home-based with a focus on promoting quality of life.
We sincerely hope that this rebranding results in more people receiving the support that they so desperately need during some of the most difficult times in a person’s life.”
The National Treasury’s Cost Containment Letter sent to government departments instructing, among others, the freezing of posts was one of the big themes underlying talks about building South Africa’s healthcare worker capacity during the Public Health Association of South Africa’s (PHASA) conference held recently in Gqeberha.
With Finance Minister Enoch Godongwana expected to deliver the medium-term budget policy statement on 1 November, the freezing of posts will further hamstrung already strained health services, some presenters at the conference warned.
An oversight visit to TB hospitals by members of the provincial legislature (MPLs) in the Eastern Cape in the first week of September (5 to 8 September) showed just how bad the staff shortages are. The only remaining hospital in Nelson Mandela Bay dedicated to TB services, Jose Pearson Hospital in Bethelsdorp, has had staff vacancies hovering around 20% since 2019. The hospital provides dedicated TB services to the western part of the province. MPLs heard that in some other hospitals, vacancy rates are even higher, and non-filling of critical posts in some cases results in further medico-legal claims against the department, as the current staff buckles under massive patient loads.
Last year, in response to a parliamentary question, figures the health department released showed that there were 3 892 vacant healthcare worker posts in the province. In the nursing categories, there was a vacancy rate of 15.3%. For paramedics (EMS) the vacancy rate was 10.7%, medical practitioners 8.4%, and pharmacists 13.7%. By June this year, in another response relating to specialist nurses, the vacancy rate in the province had dropped to 13%.
Dr Prudence Ditlopo Senior Researcher at the University of the Witwatersrand, was presenting her research on the impact of nurse workloads and professional support on healthcare outcomes at the PHASA conference. Ditlopo said nurses already have a huge workload and issues around budget cuts impact morale. “I am sure they are asking themselves what will happen to [them] when we [they’re] already understaffed.
“This is not the first time that this monotonous cycle has been happening. Yes, we understand the economic side of it, but at the very same time, what does it say about the well-being of the nurse practice environment, the patients, and the quality of patient care? If nurses see that they are overwhelmed by the workload, they will make sure to find ways that will enable them to cope.
“Enable them to cope” means nurses will find a way that works for them. If what works for them is only seeing ten patients per day, they will do that and they will be gatekeepers for other patients who are coming to the facility. That alone will influence the quality and standard of care in primary care in South Africa,” said Ditlopo.
‘Will create more problems’
Dr Busisiwe Matiwane of the University of The Witwatersrand’s School of Public Health also weighed in on the implications of the Treasury letter.
“In the current system, health professionals have to work for the government to fulfil their community service obligations. However, it can be challenging for them to be assigned to specific hospitals when it is time for their community service. Additionally, with the government announcing a freeze on posts, many individuals who are not government-funded may be compelled to seek employment outside of the government after completing their community service,” Matiwane told delegates.
“If these posts are indeed frozen, does that mean that the government will also halt the placement of individuals who are required to complete community service? The current structure dictates that if you fail to fulfil your community service, you will not be recognised by the statutory bodies as an independent practitioner.
“The implication of this proposal by the government will create more problems, as we already face the challenge of health professionals’ placement or their community services,” she said. “The main concern is whether the posts will be frozen and what will be done. I think this concern has raised questions for many people, who wonder what it means if they are unable to complete their community service or the internship. Does it mean they cannot work?” she asked.
‘protect what is already there’
Speaking on the sidelines of the three-day conference, director of the Rural Health Advocacy Project, Russell Rensburg, said the wage agreement on a 4.5% increase for the public sector had Treasury’s back against the wall since that was not budgeted for in their February budget.
“Treasury is playing hardball and the provinces must decide what they need. The national government must also decide what they need. If they follow through on this, they won’t be able to sustain the public health system. There is concern that doctors will leave as part of cost containment measures, and you can’t run a healthcare system without healthcare workers. But we will only know the true position of the Treasury when they publish the medium-term budget policy statement,” said Rensburg.
“I believe at the moment they are just testing the market. They are saying we must have one thing, but we can’t have both, so that is the game they are playing. Our position is clear on this issue. Before any salary cuts or job freezes, we need to protect what is already there. We need to retain this year’s cohort of community service doctors, pharmacists, and nurses because these people helped us during COVID-19. Some were interns during COVID-19 and they are the core that can build the health service in the post-COVID-19 era. So, the immediate priority is to retain those posts because we don’t know if there will still be community service going forward,” said Rensburg.
‘working with what we have’
Several speakers and presenters at the PHASA conference raised concerns about the existing scarcity of healthcare workers and urged the Department of Health to take action. The experts, academics, researchers, students, non-governmental organisations, and civil society members all agree that healthcare is a fundamental human right, but that right won’t be fulfilled without healthcare workers, as there cannot be health services without workers. The government’s key policy document on human resources for health warned as far back as 2020 that the country is facing a critical shortage of healthcare workers.
Dr Krish Vallabhjee, former Chief Director of Strategy and Health Support in the Western Cape Health Department, believes that management must use whatever resources are available to achieve good results.
Vallabhjee said, “Budget cuts are a reality, so whatever we talk about here and in many of these conference sessions, we can’t be talking about wanting more and more. We need to work with what we have. How can we repurpose the people we have? Can’t we use them more effectively to achieve the same effect?” he asked.
“Managers need to work with their staff instead of just sitting in some corner and making budget cut decisions. Managers need to engage with staff to address the problem of not having enough budget. How do we work together? What are our priorities? As managers, we must listen to what people are saying on the ground. What are the doctors, nurses, and local managers saying? We must be united. [It should not be a thing that one hospital, clinic, and the district [are] fighting for their own piece. We are one department and we have this problem of a budget. How do we unite and do the best we can?”
Government will clarify
In a cabinet statement issued on 14 September, Minister in the Presidency, Khumbudzo Ntshavheni said that Finance Minister Enoch Godongwana would clarify the cost-containment letter issued on August 31.
“Cabinet appreciates the current fiscal constraints which are not unique to South Africa but have resulted in budget shortfall. Cabinet has iterated that measures to address the budget shortfall must not impact negatively on service delivery. The Minister of Finance will shortly issue guidelines clarifying the unintended misunderstanding arising from the Cost Containment Letter issued on 31 August 2023. In addition, as part of the in-year performance review of progress in implementation priorities agreed to with Ministers, the President, and Deputy President will meet with individual Ministers to ensure that fiscal management does not derail the agreed to priorities.”
Acute gastroenteritis is a common infectious disease in children aged under 6 years. Although it often resolves on its own, it has a high consultation rate in primary care, especially during out-of-office hours. In a study published in The Annals of Family Medicine, Dutch researchers interviewed parents who contacted GPs outside of normal hours, and found that who felt misunderstood or ignored were more likely to request a visit.
The researchers conducted 14 semi-structured interviews with parents who contacted primary care physicians outside of normal operating hours seeking medical attention for their children. They sought to explore parental motivations, expectations, and experiences of off-hours primary care contacts for children with acute gastroenteritis. Parents were more likely to contact their primary care physician after hours when their child exhibited unusual behaviour, to prevent symptom deterioration, and to gain medical reassurances.
The researchers reported that parents expected their doctors to perform a thorough physical examination, provide information, and make follow-up care agreements. Parents reported dissatisfaction if they felt their doctors didn’t listen to them, misunderstood them, or didn’t take them seriously. This increased their likelihood of seeking another consultation. Researchers concluded that there is often a mismatch between parental expectations and GPs’ actions. Greater awareness and understanding on the part of GPs about the feelings and expectations of parents could guide them in interacting with parents, which may improve satisfaction with primary health care and reduce after-hours care requests.
The researchers found that among parents who requested out-of-office consultations for their children who were experiencing gastroenteritis, those that felt misunderstood or not listened to by their doctors were more likely to request such a visit. Taking greater account and understanding about parents’ feelings and expectations about care for their child may improve satisfaction with primary health care, specifically with requests that come in after normal clinic hours.
In a new study using mice, neuroscientists have uncovered a crucial component for restoring functional activity after spinal cord injury. In the study, published in Science, the researchers showed that re-growing specific neurons back to their natural target regions led to recovery, while random regrowth was not effective.
In a 2018 study in Nature, the team identified a treatment approach that triggers axons to regrow after spinal cord injury in rodents. But even as that approach successfully led to the regeneration of axons across severe spinal cord lesions, achieving functional recovery remained a significant challenge.
For the new study, the team of researchers from UCLA, the Swiss Federal Institute of Technology, and Harvard University aimed to determine whether directing the regeneration of axons from specific neuronal subpopulations to their natural target regions could lead to meaningful functional restoration after spinal cord injury in mice. They first used advanced genetic analysis to identify nerve cell groups that enable walking improvement after a partial spinal cord injury.
The researchers then found that merely regenerating axons from these nerve cells across the spinal cord lesion without specific guidance had no impact on functional recovery. However, when the strategy was refined to include using chemical signals to attract and guide the regeneration of these axons to their natural target region in the lumbar spinal cord, significant improvements in walking ability were observed in a mouse model of complete spinal cord injury.
“Our study provides crucial insights into the intricacies of axon regeneration and requirements for functional recovery after spinal cord injuries,” said Michael Sofroniew, MD, PhD, professor of neurobiology at the David Geffen School of Medicine at UCLA and a senior author of the new study. “It highlights the necessity of not only regenerating axons across lesions but also of actively guiding them to reach their natural target regions to achieve meaningful neurological restoration.”
The authors say understanding that re-establishing the projections of specific neuronal subpopulations to their natural target regions holds significant promise for the development of therapies aimed at restoring neurological functions in larger animals and humans. However, the researchers also acknowledge the complexity of promoting regeneration over longer distances in non-rodents, necessitating strategies with intricate spatial and temporal features. Still, they conclude that applying the principles laid out in their work “will unlock the framework to achieve meaningful repair of the injured spinal cord and may expedite repair after other forms of central nervous system injury and disease.”
‘Long COVID’ is a mysterious constellation of symptoms associated with having recovered from COVID infection – but how many cases represent a true condition, and how many fall under a poorly-defined umbrella of currently known ones? Overly broad definitions, a lack of appropriate, or any, comparison groups, among other things, in studies looking at the epidemiology of the condition have distorted the risks, say the authors of a review published in BMJ Evidence-based Medicine.
This is further compounded by inclusion of poorly conducted studies into systematic reviews and pooled data analyses that end up overstating the risk yet again, they add.
Likely consequences include increased public anxiety and healthcare spend; misdiagnoses; and diversion of funds from those who really do have other long term conditions secondary to COVID infection, suggest the researchers.
Many after-effects of COVID infection include post-ICU syndrome, which is a constellation of health issues that are present when the patient is in intensive care and which persist after discharge home, and shortness of breath following pneumonia. The trouble is that these are common to many upper respiratory viruses, the researchers point out.
None of the working definitions of ‘long COVID’ used by influential health bodies, such as the US Centers for Disease Control and Prevention, the World Health Organization, the UK National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), and the Royal College of General Practitioners requires a causal link between SARS-CoV2 and a range of symptoms.
Not only should comparator (control) groups be included in ‘long COVID’ studies, when they often aren’t, but they should also be properly matched to cases, ideally by age, sex, geography, socioeconomic status and, if possible, underlying health and health behaviours, which they rarely are, say the researchers.
During the early stages of the pandemic, when SARS-CoV-2 testing wasn’t widely available, studies were more likely to include a non-representative sample of SARS-CoV-2-positive patients by including fewer patients with mild or no symptoms.
This is known as sampling bias, which occurs when certain members of a population have a higher probability of being included in a study sample than others, potentially limiting the generalisability of a study’s findings, explain the researchers.
“Our analysis indicates that, in addition to including appropriately matched controls, there is a need for better case definitions and more stringent [‘long COVID’] criteria, which should include continuous symptoms after confirmed SARS-CoV-2 infection and take into consideration baseline characteristics, including physical and mental health, which may contribute to an individual’s post COVID experience, “ they write, adding that the umbrella term ‘long COVID’ should be jettisoned in favour of different terms for specific after effects.
While the results of high quality population studies on ‘long COVID’ in adults and children have been reassuring, they point out, the body of research “is replete with studies with critical biases” they add, setting out common pitfalls.
“Ultimately, biomedicine must seek to aid all people who are suffering. In order to do so, the best scientific methods and analysis must be applied. Inappropriate definitions and flawed methods do not serve those whom medicine seeks to help,” they insist.
“Improving standards of evidence generation is the ideal method to take long COVID seriously, improve outcomes, and avoid the risks of misdiagnosis and inappropriate treatment,” they include.
Professor Valerie Mizrahi, a world-leading tuberculosis researcher and director of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, is retiring at the end of the year. PHOTO: Nasief Manie/Spotlight
World-leading tuberculosis researcher Professor Valerie Mizrahi was 35 when her mother Etty started losing weight and coughing furiously. After healthcare professionals in Johannesburg failed to accurately diagnose her, it was a doctor in Plettenberg Bay who told Etty: “The good news is you don’t have lung cancer, the bad news is that you have tuberculosis (TB).”
At the time, Mizrahi’s two infant daughters – aged one and three years old – had been spending much time with their granny. And so Mizrahi found herself crushing TB prevention tablets into her children’s porridge with honey.
Etty was treated at the then-Rietfontein Hospital, the precursor to Sizwe Tropical Diseases Hospital in Johannesburg. “My mom got very ill,” recalls Mizrahi. “She almost died of TB. And then 10 years later, she had to have a lobe from one of her lungs removed because she was one of those unfortunate people who got post-TB fibrosis.”
This was the early 1990s. Mizrahi was then with the South African Institute for Medical Research (SAIMR) linked to the University of the Witwatersrand, where she established the Molecular Biology Unit. She had identified TB as a lurking problem in South Africa, particularly in mines and in hospitals, calling it “a worthy foe ripe with opportunity for scientific investigation” – a problem she felt not enough people were talking about. It had been a pivotal moment when TB entered her own home, one that she says galvanised her thinking.
“It was a dramatic eye-opener for me as a basic scientist,” she says. “It was traumatic because of the time it happened in my career. Our family suddenly being thrust into the world of TB control. We had all these questions like we didn’t know where my mum got it, was her TB drug-susceptible, and why it would take so long to find this out. I got to see first-hand how difficult it was to get answers…”
Born in 1958 to Etty and Morris in Harare, Zimbabwe, Mizrahi studied at the University of Cape Town (UCT), forging an unusual career path, veering from mathematics and chemistry to biochemistry, genetics, and microbiology. In a male-dominated field, she became one of the first in South Africa to interrogate TB at a basic science level – that is to say, research aimed at advancing our understanding of the basic science of how TB bacteria survive, replicate, and resist attempts to kill it.
‘the only good TB bacillus is a dead one’
Discussing TB, Mizrahi’s passion is effervescent, her every second sentence punctuated with “okay”. These underscore her statements – subtle pauses allowing for her preceding words to sink in.
Source: CC0
…there’s a reason why TB has persisted for so long. The bacillus is pretty hard to kill. It’s built like Fort Knox.
Prof Valerie Mizrahi
A particular interest for Mizrahi is developing antibiotics “that can kill this bacterium stone cold dead”.
“To me, the only good TB bacillus is a dead one,” she says. “But there’s a reason why TB has persisted for so long. The bacillus is pretty hard to kill. It’s built like Fort Knox. So it’s a monumental challenge. We don’t know where all the bacteria are residing. We know that TB in an infected lung is sitting in really difficult places, hard places for drugs to get to. This notion of going after the bacillus with drugs and just slamming it is a tough problem. Not insurmountable, but there’s a lot of research that needs to be done.”
TB can be cured, but treatment typically takes at least six months and involves taking at least four different antibiotics, with side effects ranging from minor to serious. In addition to research on new antibiotics, there are also several experimental TB vaccines currently in late-phase studies. The only TB vaccine we have was developed more than a century ago and only has some moderate efficacy in kids.
The IDM
Since 2011 Mizrahi has served as director of the Institute of Infectious Disease and Molecular Medicine (IDM) – the University of Cape Town’s (UCT) largest cross-faculty research unit with over 800 affiliated staff and grants running into hundreds of millions of rands.
Mizrahi’s glass-encased office looks directly onto Table Mountain and hospital bend – where, at the time of our interview, N2 traffic out of Cape Town is already at a standstill. Behind her desk, Mizrahi quips. “Yes, this is the most beautiful office at UCT, everyone agrees…” Below, students can be seen milling about on the health sciences campus.
Last year in its Best Global Universities 2022-2023 survey, online portal US News ranked UCT as 24th best university in the world for studying infectious diseases. Mizrahi is ambivalent about the IDM taking credit for this accolade. She notes that this success is founded on problems of a “confounding and overwhelming” scope, with many diseases being proxies for poverty and inequality in South Africa.
The IDM’s focus includes TB, HIV/AIDS, COVID-19, other infectious diseases like sexually transmitted infections, and non-communicable diseases such as preventable cancers, cardiovascular, and psychiatric disorders.
Reflecting on the IDM, she says they have accrued a “research ecosystem – a concentration of expertise, something resembling critical mass” – bringing together specialists across the basic, clinical, and public health sciences, in one place.
“We’ve got Groote Schuur Hospital across the road,” she says. “We have geneticists and biochemists, virologists, and immunologists. There’s a clinician across the corridor from me, bioinformaticians, and microscopists downstairs. If you are the kind of researcher who revels in asking questions and finding people who can answer them, then this is the place for you.”
Going forward, multi-disciplinary research is what excites her. “HIV and TB have been so dominant in the narrative of this country. But now when you look at the figures and the data, we are dealing with a huge burden of non-communicable disease on top of infectious diseases,” she says. “The key question moving forward is how not to think in silos.”
Polymaths and dilettantes
This, she says, takes humility.
“To do this, one has to be very humble. You need to know what you don’t know. People who work really well in interdisciplinary spaces are those who understand the limits of their own specialist knowledge, and the need to listen to where another person is coming from.”
She distinguishes between polymaths and dilettantes. “You have to be careful not to be a dilettante, who knows a little about a lot. Research can be very superficial in that way. So I have my antenna out all the time to distinguish between polymaths, who really are people who know a lot about a lot, and dilettantes who know a little about a lot. And well, in this institute we have a lot of polymaths, brilliant researchers who move across disciplines, very interesting people to work with.”
With a string of awards and an A1-rating from South Africa’s National Research Foundation, earlier this year, Mizrahi was elected a fellow of the Royal Society, the United Kingdom’s National Academy of Sciences. However, she recalls humbling moments along the way – like the time she flew to London seven months pregnant with her second child, for her first-ever interview with the Wellcome Trust committee to secure funding. “I was so confident, but I was ill-prepared,” she says. “They savaged me! I tried to frame it not as a failure but as a learning experience.”
Passing the baton
At the end of this year, Mizrahi will pass on the baton when she retires. Of her achievements, she is proudest of young scholars she has helped to shape. “Their legacies will last much longer than a few more citations of a publication,” she says.
Mizrahi notes more and more women leaders in her field. For example, recently, while delivering a talk at the Weizmann Institute in Israel, she noticed chemist and Nobel laureate Ada Yonath in the room. “Talk about a role model; I was almost in tears.”
Studying at UCT, Mizrahi’s own mentors had mostly been men – something she didn’t even notice, she says, as male professors treated her no different. What did cut her was racial segregation at the time, prompting a political awakening and stints leaving South Africa to work in the United States. First as a postdoctoral fellow at Pennsylvania State University and then at drug company, SmithKline & French in Philadelphia.
Her own background makes her sensitive to marginalised groups, she says. Her grandparents were Sephardi Jews who fled Rhodes Island, today part of Greece, ten years before World War II, to find refuge in Zimbabwe.
Having just read former UCT vice-chancellor Max Price’s book Statues and Storms: Leading a University Through Change, she says, “It took me back to some very difficult times. It’s harrowing and brave and made me realise that even though I was here in the midst of it [#feesmustfall and #rhodesmustfall protests], a senior person of the university, how little I really knew of what was going on. It really is a lesson in crisis leadership.”
There’s no control experiment to life, you can’t go back and redo it.
Mizrahi lives in Sea Point with her one daughter. Her other daughter is based in Vancouver. Here, she likes to park her car at the end of the week, walking around – “either listening to a New York Times podcast or a beautiful piece of music and that’s when I think.”
She describes herself as an introvert who needs personal time to stay sane. She is deeply thoughtful about her roots, wondering about a sense of belonging. “As white people in Africa, I think this is part of the reckoning we go through. I truly identify as being African. Arriving at Johannesburg, just breathing in the air, it feels like home.”
Looking back, Mizrahi notes her mother as a major influence in her life. “Not a highly educated woman. But the wisest, smartest person I know.” Etty still lives in Johannesburg while Morris has passed away. To this day, Etty thinks of herself as a proud TB survivor, says Mizrahi.
On her retirement, the scholar says, “Now it’s about opening up opportunities for others, writing a few papers, and contributing to the TB drug discovery space.”
“I’ve done the best I can,” she says, “I don’t believe in having regrets… There’s no control experiment to life, you can’t go back and redo it. But I don’t know that I could have done it any differently.”
Presenting its financial year-end results to investors and analysts, Discovery Group has reported profit increases of 24% across all of its opertaions. CEO Adrian Gore commented, “Discovery’s three business composites – South Africa, United Kingdom and Vitality Global – delivered excellent performances in line with the Group’s strategy and ambition.”
For the reporting period, Discovery posted an increase in normalised profit from operations, up 24% from R9 384 million to R11 661 million. Headline earnings increased by 5% to R5 490 million; normalised headline earnings increased by 32% to R7 678 million; and core new business annual premium income (API) rose 12% to R22 788 million. Embedded value increased to R98 176 million, which represented a 13.2% return on embedded value.
In a year characterised by significant macroeconomic uncertainty, Discovery continued its focus on delivering quality earnings and cashflow with a strong balance sheet; while following a clear growth strategy for each composite (SA, UK and Vitality Global). The Group invested in its proprietary Vitality Shared-value model, and intensified the focus on key initiatives while closing business areas with marginal benefits.
The Group remained financially resilient with high levels of liquidity and the financial leverage ratio (FLR) improving to 20%. Organic cash generation was robust during the year following growth in quality earnings, a significant recovery in Discovery Life’s cash generation following elevated COVID-19-related claims in the previous reporting period, and the reduction in the cost of new initiatives. The robust balance sheet and cash positions support the resumption of dividends, and the directors declared a final gross cash dividend of 110 cents per ordinary share.
Discovery’s saw excellent results for each composite. The SA Composite’s normalised operating profit increased by 22% to R9 096 million and new business by 11% to R16 818 million. Discovery Health showed strong growth across all metrics with prior investment in technology driving efficiencies and continued innovation. Discovery Life had a resilient performance with positive variances, with Group Life returning to profit. Discovery Invest generated significant growth in profit, given higher investment markets and other in-period gains. Discovery Insure delivered on its profit turnaround, following actions taken in previous periods. Discovery Bank continued with excellent progress across all metrics, as acquisition of quality clients accelerated over the year.
Normalised operating profits rose by 14% for the UK Composite and 49% for Vitality Global (US$44 million), driven by especially strong results from China.
Gore concluded, “Discovery’s growth strategy is based on the efficacy, repeatability, and scalability of our Vitality Shared-value model. It is a powerful platform from which to drive new business and enables us to pursue growth through our organic businesses and global partnerships. The Group is now focused on evolving the model into an integrated value chain with bespoke modules to drive growth and market leadership across each of the composites.”
Positive results from a clinical trial comparing the safety and efficacy of ciclosporin with methotrexate in children and adolescents with severe dermatitis will likely change treatment paradigms for this debilitating skin condition, its researchers have said. The trial, published in the British Journal of Dermatology, also examined whether the severity of the disease changed or returned after treatment ended.
For children and young people with atopic dermatitis, the most common skin condition in children, the main first line conventional systemic treatments are methotrexate and ciclosporin, two immuno-modulatory drugs.
There have been no adequately powered randomised clinical trial evidence for safety and treatment success for paediatric patients with this condition, and with new therapies being introduced at a high cost, establishing a gold standard for treatment with the conventional systemic therapies like methotrexate and ciclosporin is needed.
The trial, led by King’s College London, assessed 103 children with severe atopic dermatitis age 2–16 years across 13 centres in the UK and Ireland. The patients were given oral doses of methotrexate or ciclosporin and assessed over nine months of treatment and six months after the therapy ended.
The study found that ciclosporin works faster and reduces disease severity more at 12 weeks but was more expensive, whereas methotrexate was significantly cheaper and led to better objective disease control after 12 weeks and off therapy, with fewer participant-reported flares of atopic dermatitis after treatment had stopped. There were also no concerning safety signals.
Based on the TREAT trial findings, methotrexate is a useful and safe treatment in paediatric patients with severe atopic dermatitis and a good alternative to ciclosporin, especially in settings where health care resources are limited.
Professor Carsten Flohr, Chair in Dermatology and Population Health Sciences at King’s College London, and consultant dermatologist at St John’s institute of dermatology, Guy’s and St Thomas’ NHS Foundation Trust, said:
“This is the largest paediatric trial using conventional immuno-modulatory treatments in severe atopic dermatitis and was conducted across 13 centres in the UK and Ireland and is likely to change our treatment paradigm around this condition, not just for patients in the UK but also internationally.”
