Day: July 24, 2024

“Not Being Afraid to Speak out, it does get me into Trouble Quite Often,” Says Prof Shabir Madhi

Professor Shabir Madhi of Wits University. Photo: supplied.

By Biénne Huisman

Amid the uncertainty of the early days of the COVID-19 pandemic, Professor Shabir Madhi often stood out for his clarity of thought in making sense of rapidly evolving scientific evidence. Biénne Huisman chatted to Madhi about vaccines, ongoing challenges with the Gauteng health department, and being outspoken about issues such as the war in Gaza.

Professor Shabir Madhi became known to many in South Africa for leading the charge in two of the first COVID-19 vaccine clinical trials conducted in Africa – those for the AstraZeneca and Novavax vaccines. At a time of much scientific uncertainty, he was often quoted in the press – gaining a reputation for keeping his cool and calling things as he saw them based on available evidence.

He spoke out against the politicisation of science and was a staunch advocate for access to vaccines, especially for older people at higher risk of severe illness and death. He wasn’t afraid to ruffle feathers, openly criticising government’s COVID-19 vaccine communication efforts and arguing that government should take vaccines to the people, rather than the other way around. He called for the ending of strict lockdowns, before many others did so. Reflecting on his reputation for not holding back on his beliefs, he admits to “having a short fuse, especially when people are talking nonsense – or what I consider to be entirely off the mark”.

What may be less obvious to the public, is that Madhi’s healthcare impact precedes COVID by decades.

Internationally respected for his research into paediatric infectious diseases, his work has helped to save the lives of hundreds of thousands of children and informed World Health Organization policy (WHO) – notably relating to the pneumococcal conjugate vaccine (to prevent pneumonia and meningitis) and the rotavirus vaccine (to prevent diarrhoeal disease in young children).

His work continues. Just last year a landmark study, led in South Africa by Madhi’s Vaccines and Infectious Diseases Analytics Research Unit at the University of the Witwatersrand (Wits), found that immunisation of pregnant women safely protected their unborn babies from respiratory syncytial virus (RSV). As Spotlight reported at the time, researchers estimate the vaccine can save thousands of young lives.

Speaking to Spotlight over Zoom from Wits in Johannesburg, where he is Dean of Health Sciences, Madhi relays his love of treating kids – who “most importantly, don’t lie, and who are the most vulnerable”.

“Accidental vaccinologist”

Madhi has been described as an “accidental vaccinologist”. Shrugging inside a navy suit, he says he never intended to become a physician, let alone a professor in vaccinology. At medical school at Wits, he nearly dropped out after a month.

As a child, growing up in Lenasia, Madhi wanted to become an engineer. But born to a mathematics teacher father and a stay at home mum, money was tight. His only opportunity to attend university presented itself via a bursary in medicine.

“I only really started to enjoy medicine once I specialised in paediatrics,” he says. “But more importantly, that’s when I realised the huge potential that existed in medicine to make a difference, particularly the potential for vaccines to make a big difference over a short period of time – not on an individual level, but at a community level. And that’s what really drove me into the space of research.”

While doing his peadiatric training at Chris Hani Baragwanath Academic Hospital (he obtained a master’s degree in paediatrics from Wits in 1998), it struck him that the leading causes of death among children were entirely preventable.

“Back then, close to 750 000 children were dying of measles globally; half of those deaths were happening in Africa, despite the vaccine for measles being available since the 1970s. South Africa was one of the countries with a poor public immunisation programme; up until 1992 South Africa didn’t have a public immunisation programme.”

In 2009, in a first on the African continent, pneumococcal and rotavirus vaccines were finally officially rolled out in South Africa.

“While I was training at Baragwanath, there was a ward just for children with gastroenteritis or diarrhoea,” he recalls. “But six months after we introduced the rotavirus vaccine in South Africa [in 2009], we shut down the diarrhoea ward at Baragwanath and probably every other diarrhoea ward in the country.”

Contributing internationally

Today Madhi’s CV is long. He sits on scores of scientific advisory committees, attending conferences and delivering talks around the world.

Since 2019, he has served on a global panel of experts convened by the WHO, the Strategic Advisory Group of Experts on Immunization (SAGE), of which he now is deputy chair. He also chairs the SAGE working group on polio.

“I’m really enjoying SAGE at the moment,” he says. “This is where I think I am making a meaningful contribution. It really is an eye opener to the different types of research that’s taking place globally; but also the type of challenges we face in terms of ensuring that children are adequately immunised.

“It’s great to be working on new vaccines, coming up with new vaccines; but that’s a meaningless exercise unless you can ensure that those vaccines are getting into the arms of children – because that is what saves lives. So yes, dealing with issues around implementation and advocacy.”

SAGE requires frequent trips to Geneva, where the WHO is based.

Our discussion turns to business travel – the amount required for a researcher to remain “relevant and competitive”. With typical candour, Madhi outlines challenges faced by researchers from the global south.

“I think coming from South Africa, coming from the African continent, it’s more of a challenge for researchers to establish themselves, for a number of reasons. Firstly to become known in the international space, you probably need to deliver so much more than what is expected from our northern hemisphere counterparts.

“Then in addition to the inconvenience of needing to travel so often, there are subtle things which people in the northern hemisphere don’t have to deal with. Needing to get visas and dealing with customs officials when entering countries.

“It can become an extremely unpleasant experience, and you really need to swallow your pride given what is blatant racism at times. For example, nowadays I refuse to fly through Germany because the customs office in Frankfurt is probably the worst I have encountered. All of a sudden, they would keep me and question me for both arrival, as well as departure…”

Local challenges

The discussion turns back to South Africa, and health challenges in his home province of Gauteng. Here also Madhi has tried to make a difference, but it hasn’t been plain sailing.

Commenting on a floundered memorandum of agreement (MOA) signed between Wits and the Gauteng Department of Health in June 2022, Madhi says: “The bottom line unfortunately; the Gauteng Department of Health simply doesn’t have stability of leadership. At the level of the MEC in particular; I mean since I’ve been dean, there’s been about four or five heads of department. And it becomes difficult to follow through with any of these programmes.”

Madhi adds that Wits university executives had worked on the memorandum for seven years. The agreement set out a plan to combine university and government resources in “academic health complexes” for enhanced service delivery. But the Department of Health put it on hold three months later, following a related Public Service Commission inquiry.

He explains: “They convened this big workshop, spending probably a mini fortune, to basically facilitate the establishment of an MOA, not just between Wits and the Department of Health, but between the Department of Health and many other academic hospitals in the province. Because of the intervention, the Department of Health indicated that they weren’t going to implement our MOA until that particular commission concluded their work. But since then, there’s been absolutely no report from that meeting.”

Not afraid to speak out

On social media, Madhi speaks out about atrocities being committed in Gaza.

To Spotlight, he says leadership holds no place for neutrality.

“As part of leadership, and I do consider myself a leader in the different roles that I play – either in my research unit or currently as university dean – you need to be prepared to take a stance. You can’t remain neutral on positions. You need to interrogate facts. And once having interrogated the facts, you need to reach a conclusion; then follow through with what is required, if there’s anything that needs to be implemented.”

Madhi says his leadership style was honed during childhood. “Not being afraid to speak out, it does get me into trouble quite often,” he says, laughing. “I think that’s just part of my upbringing, being an activist during apartheid in the Lenasia Youth League and other activist organisations. My upbringing was, when things are not what it’s meant to be, you speak out; you champion the right cause.”

These days Madhi lives in Northcliff with his wife, with whom he has two children. His favourite football team is Arsenal and a book he says he recently enjoyed was The Covenant of Water – a three generation family account set in India, by physician and author Abraham Verghese.

Republished from Spotlight under a Creative Commons licence.

Read the original article

Ancient Virus DNA Lurking in Human Genome Fuels Modern-day Cancers

Photo by Sangharsh Lohakare on Unsplash

Peek inside the human genome and, among the 20 000 or so genes that serve as building blocks of life, you’ll also find flecks of DNA left behind by viruses that infected primate ancestors tens of millions of years ago.

These ancient hitchhikers, known as endogenous retroviruses, were long considered inert or “junk” DNA, defanged of any ability to do damage. New CU Boulder research reported in Science Advances shows that, when reawakened, they can play a critical role in helping cancer survive and thrive. The study also suggests that silencing certain endogenous retroviruses can make cancer treatments work better.

“Our study shows that diseases today can be significantly influenced by these ancient viral infections that until recently very few researchers were paying attention to,” said senior author Edward Chuong, an assistant professor of molecular, cellular and developmental biology at CU Boulder’s BioFrontiers Institute.

Studies show about 8% of the human genome is made up of endogenous retroviruses that slipped into the cells of our evolutionary ancestors, coaxing their hosts to copy and carry their genetic material. Over time, they infiltrated sperm, eggs and embryos, baking their DNA like a fossil record into generations to come – and shaping evolution along the way.

Even though they can no longer produce functional viruses, Chuong’s own research has shown that endogenous retroviruses can act as “switches” that turn on nearby genes. Some have contributed to the development of the placenta, a critical milestone in human evolution, as well as our immune response to modern-day viruses like COVID.

“There’s been a lot of work showing these endogenous retroviruses can be domesticated for our benefit, but not a lot showing how they might hurt us,” he said.

Switching cancer genes on

To explore their role in cancer, Chuong and first author Atma Ivancevic, a research associate in his lab, analyzed genomic data from 21 human cancer types from publicly available datasets. 

They found that a specific lineage of endogenous retrovirus known as LTR10, which infected some primates about 30 million years ago, showed surprisingly high levels of activity in several types of cancer, including lung and colon cancer. Further analysis of tumors from dozens of colorectal cancer patients revealed that LTR10 was active in about a third of them.

When the team used the CRISPR gene editing tool to snip out or silence sequences where it was present, they discovered that critical genes known to promote cancer development and growth also went dark.

“We saw that when you silence this retrovirus in cancer cells, it turns off nearby gene expression,” said Ivancevic.

Experiments in mice yielded similar results: When an LTR10 “switch” was removed from tumor cells, key cancer-promoting genes, including one called XRCC4, switched off too, and treatments to shrink tumors worked better. 

“We know that cancer cells express a lot of genes that are not supposed to be on, but no one really knows what is turning them on,” said Chuong. “It turns out many of the switches turning them on are derived from these ancient viruses.”

Notably, the endogenous retrovirus they studied appears to switch on genes in what is known as the MAP-kinase pathway, a famed cellular pathway that is adversely rewired in many cancers. Existing blockbuster drugs on the market, known as MAP-kinase inhibitors, likely work, in part, by disabling the endogenous retrovirus switch, the study suggests.

Reawakening ancient viruses

The authors note that just this one family of retrovirus regulates as many as 70 cancer-associated genes in this pathway. Different lineages likely influence different pathways that promote different cancers.

The team plans to look into some of them next.

“Any time we can find out how genes or pathways that are inherently altered in tumours are regulated, that is really helpful,” said co-author Todd Pitts, associate professor of medical oncology with the CU Cancer Center on the Anschutz Medical Campus. “It allows us to potentially find new therapies or find patients that might respond better to current therapies.”

The study is not the first to implicate ancient viruses in cancer. Previous studies suggest they may emit toxic compounds or spark genetic mutations. And two other recent studies show that they switch on cellular pathways in leukaemia and prostate cancer.

Chuong said that while these shadow viruses are likely an underappreciated source of genetic influence across all cancer types, this study doesn’t show they cause cancer. Rather, cancer itself wakes them up, empowering them to activate other disease-promoting processes to help keep it alive.

He suspects that as people’s cells age, their genomic defenses break down, enabling other ancient viruses to reawaken and contribute to other health problems too. 

“The origins of how diseases manifest themselves in the cell have always been a mystery,” said Chuong. “Endogenous retroviruses are not the whole story, but they could be a big part of it.”

Source: University of Colorado Boulder

Less Invasive Method for Measuring Intracranial Pressure After TBI

Coup and contrecoup brain injury. Credit: Scientific Animations CC4.0

Researchers at Johns Hopkins explored a potential alternative and less-invasive approach to evaluate intracranial pressure (ICP) in patients with serious neurological conditions. This research, using artificial intelligence (AI) to analyse routinely captured ICU data, was published in Computers in Biology and Medicine.

ICP is a physiological variable that can increase abnormally if one has severe traumatic brain injury, stroke or obstruction to the flow of cerebrospinal fluid. Symptoms of elevated ICP may include headaches, blurred vision, vomiting, changes in behaviour and decreased level of consciousness. It can be life-threatening, hence the need for ICP monitoring in selected patients who are at increased risk. But the current standard for ICP monitoring is highly invasive: it requires the placement of an external ventricular drain (EVD) or an intraparenchymal brain monitor (IPM) in the functional tissue in the brain consisting of neurons and glial cells by drilling through the skull.

“ICP is universally accepted as a critical vital sign – there is an imperative need to measure and treat ICP in patients with serious neurological disorders, yet the current standard for ICP measurement is invasive, risky, and resource-intensive. Here we explored a novel approach leveraging Artificial Intelligence which we believed could represent a viable noninvasive alternative ICP assessment method,” says senior author Robert Stevens, MD, MBA, associate professor of anaesthesiology and critical care medicine.

EVD procedures carry a number of risks including catheter misplacement, infection, and haemorrhaging at 15.3 %, 5.8 %, and 12.1 %, respectively, according to recent research. EVD and IPM procedures also require surgical expertise and specialised equipment that is not consistently available in many settings thus underscoring the need for an alternative method in examining and monitoring ICP in patients.

The Johns Hopkins team, a group that included faculty and students from the School of Medicine and Whiting School of Engineering, hypothesised that severe forms of brain injury, and elevations in ICP in particular, are associated with pathological changes in systemic cardiocirculatory function due, for example, to dysregulation of the central autonomic nervous system. This hypothesis suggests that extracranial physiological waveforms can be studied to better understand brain activity and ICP severity.

In this study, the Johns Hopkins team set out to explore the relationship between the ICP waveform and the three physiological waveforms that are routinely captured in the ICU: invasive arterial blood pressure (ABP), photoplethysmography (PPG) and electrocardiography (ECG). ABP, PPG and ECG data were used to train deep learning algorithms, resulting in a level of accuracy in determining ICP that rivals or exceeds other methodologies.

Overall study findings suggest a completely new, noninvasive alternative to monitor ICP in patients.

Stevens says, “with validation, physiology-based AI solutions, such as the one used here, could significantly expand the proportion of patients and health care settings in which ICP monitoring and management can be delivered.” 

Source: John Hopkins Medicine

Prostate Cancer Blood Test Equally Effective Across Ethnic Groups

Photo by Nicholas Swatz

The Stockholm3 blood test, developed by researchers at Karolinska Institutet, is equally effective at detecting prostate cancer in different ethnic groups, according to a new paper published in The Journal of Clinical Oncology. The test produces significantly better results than the current PSA standard.

Stockholm3, a prostate cancer test developed in Sweden, runs a combination of protein and genetic markers from a blood sample through an algorithm to find the probability of a patient having clinically significant cancer. 

Studies in more than 90 000 men have shown that Stockholm3 produces significantly better results than the current PSA standard. The test improves prostate cancer diagnosis by reducing unnecessary MRI and biopsies and by identifying significant cancers in men with low or normal PSA values.   

Ethnically diverse group

However, previous studies have been conducted primarily in Scandinavia on a mainly White population with uncertain generalisability to the rest of the world. A Swedish-American research group has now examined how well it works in an ethnically mixed group of men in the USA and Canada. 

The study included over 2000 men at 17 different clinics, 16% of whom were Asian, 24% African-American, 14% Latin American and 46% White American.  All participants had a referral for a prostate biopsy on the basis of an elevated PSA score, abnormal rectal examination, MRI scan or other suspicious clinical finding.  

Before the biopsy was performed, a blood test was taken along with clinical data pertinent to the Stockholm3 test, which was conducted blinded to the biopsy results. 

Halving the number of unnecessary biopsies

The analysis shows that clinically relevant prostate cancer cases were found in a total of 29% of the men, somewhat more in African Americans and slightly fewer in Asians. 

It also shows that the Stockholm3 test could almost halve the number of unnecessary biopsies (45 per cent fewer: 673 as opposed to 1226) while being no less effective at detecting all clinically relevant cases. The results were similar across the different ethnic groups. 

“The study demonstrates that the Stockholm3 test is just as effective on an ethnically mixed group as it is on a White, Swedish population,” says the study’s lead author Hari T. Vigneswaran, doctor and PhD student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. 

According to him, the research answers several important questions and will lead to a more widespread use of the method: 

“Colleagues in other countries are very interested in these data, which show that Stockholm3 works for a non-Swedish population and among minorities.” 

Source: Karolinska Institutet

Opinion Piece: Claims on the Increase

Gap cover providers are seeing more claims of higher values than ever before

Photo by Cottonbro on Pexels

By Brian Harris, General Manager Operations at Turnberry

As medical inflation has continued to rise and the cost of medical procedures has increased, medical aid companies are faced with the juggling act of keeping premiums affordable while still offering adequate cover. In addition, new procedures such as robotic-assisted surgery and new cancer drugs offer better outcomes, but at a greatly increased cost.

As a result, we are seeing increased medical expense shortfalls, particularly when it comes to specialists, as well as increased co-payments and sub-limits. The upshot of this, for the consumer, is vastly increased out-of-pocket expenses, which is why gap cover has become critical. Given the increase in both the frequency and Rand value of claims, having gap cover in place has never been more important.

The state of gap cover

The frequency and value of gap cover claims have increased dramatically over the years as the gap between what medical aid covers and what specialists and providers charge continues to widen.

In 2023, Turnberry paid out R119 968 466 in claims, proportionately this accounted for 56% of the total claims, with medical aid covering the remaining 44%. This figure includes a significant number of high value claims, with many of them exceeding R100 000. Three of the highest claims in 2023 were R129 193.60 for heart disease, R128 485.43 for a nasal polyp, and R125 735.08 for a spinal fusion surgery.

These are figures paid out over the course of a single year and for a single diagnosis. Gap cover policies are subject to an overall annual limit (OAL) per individual covered by the policy, and this limit is increased in April each year, and is currently R198 660.43 per insured person. This limit resets every year, which means that over a lifetime, the amount paid out for individuals and families is far higher. At Turnberry, the top three lifetime claims are figures in the hundreds of thousands of Rands: R502 983, R450 225, and R414 331 respectively.

What does this mean for me?

The most common procedures we see as a gap cover provider are spinal disc problems, cancer, heart disease, cataract surgery and maternity, and these claims can and often do exceed R100 000 per incident. These figures highlight the fact that in South Africa, gap cover is essential for anyone wishing to access private healthcare without potentially incurring significant out of pocket expenses.

The reality is that even young and healthy people could need costly medical procedures, and as your age and life stage changes, your medical needs do too. Accidents can happen to anyone, regardless of age, and injuries related to sports and physical activity are also common in younger age groups. Starting a family inevitably involves increased medical expenses, from pregnancy and childbirth to raising children who frequently need medical attention. Health issues related to stress are also on the rise, including anxiety and depression. In later life stages, chronic diseases like high blood pressure, high cholesterol, and prediabetes become more common. Cancer can strike anyone and is increasingly seen in younger population groups.

The cost of quality medical care continues to increase, and medical expense shortfalls as well as co-payments and sub-limits are becoming more and more common, at higher amounts. This means that any medical treatment, regardless of your age or life stage, can end up costing tens of thousands of Rands out of pocket. Over a lifetime, these sums could potentially add up to millions.

It is important to engage with your broker to make sure you have the right medical aid in place first, and then to supplement this with appropriate gap cover, to ensure that you are able to access the medical care you need without the financial burden of out-of-pocket expenses resulting from medical expense shortfalls, co-payments and sub-limits.

About Turnberry Management Risk Solutions

Founded in 2001, Turnberry is a registered financial services provider (FSP no. 36571) that specialises in Accident and Health Insurance, Travel Insurance, and Funeral Cover.

With extensive experience across healthcare and insurance industries in South Africa, Turnberry offers unsurpassed service to Brokers and clients. Turnberry’s gap cover products are available to clients on all medical aid schemes, as they are independently provided and are therefore transferable in the event of a change in the client’s medical aid scheme.

Turnberry is well represented nationally, with its Head Office based in Bedfordview, Johannesburg with Business Development Managers in Cape Town and Durban. The Turnberry Team’s focus on outstanding client service comes from having extensive knowledge and experience in the financial services sector and is underwritten by Lombard Insurance Company Limited. Lombard Insurance Company Limited is an Authorised Financial Services Provider (FSP 1596) and Insurer conducting non-life insurance business.