Fever temperatures accelerate immune cell metabolism, proliferation and activity, but in a particular subset of T cells, it also causes mitochondrial stress, DNA damage and cell death, Vanderbilt University Medical Center researchers have discovered.
The findings, published in the journal Science Immunology, offer a mechanistic understanding for how cells respond to heat and could explain how chronic inflammation contributes to the development of cancer.
The impact of fever temperatures on cells is a relatively understudied area, said Jeff Rathmell, PhD, Professor of Immunobiology and corresponding author of the new study. Most of the existing temperature-related research relates to agriculture and how extreme temperatures impact crops and livestock, he noted. It’s challenging to change the temperature of animal models without causing stress, and cells in the laboratory are generally cultured in incubators that are set at human body temperature: 37°C.
“Standard body temperature is not actually the temperature for most inflammatory processes, but few have really gone to the trouble to see what happens when you change the temperature,” said Rathmell, who also directs the Vanderbilt Center for Immunobiology.
Graduate student Darren Heintzman was interested in the impact of fevers for personal reasons: Before he joined the Rathmell lab, his father developed an autoimmune disease and had a constant fever for months on end.
“I started thinking about what an increased set point temperature like that might do. It was intriguing,” Heintzman said.
Heintzman cultured immune system T cells at 39°C. He found that heat increased helper T cell metabolism, proliferation and inflammatory effector activity and decreased regulatory T cell suppressive capacity.
“If you think about a normal response to infection, it makes a lot of sense: You want effector (helper) T cells to be better at responding to the pathogen, and you want suppressor (regulatory) T cells to not suppress the immune response,” Heintzman said.
But the researchers also made an unexpected discovery: that a certain subset of helper T cells, called Th1 cells, developed mitochondrial stress and DNA damage, and some of them died. The finding was confusing, the researchers said, because Th1 cells are involved in settings where there is often fever, like viral infections. Why would the cells that are needed to fight the infection die?
The researchers discovered that only a portion of the Th1 cells die, and that the rest undergo an adaptation, change their mitochondria, and become more resistant to stress.
“There’s a wave of stress, and some of the cells die, but the ones that adapt and survive are better – they proliferate more and make more cytokine (immune signaling molecules),” Rathmell said.
Heintzman was able to define the molecular events of the cell response to fever temperatures. He found that heat rapidly impaired electron transport chain complex 1 (ETC1), a mitochondrial protein complex that generates energy. ETC1 impairment set off signalling mechanisms that led to DNA damage and activation of the tumour suppressor protein p53, which aids DNA repair or triggers cell death to maintain genome integrity. Th1 cells were more sensitive to impaired ETC1 than other T cell subtypes.
The researchers found Th1 cells with similar changes in sequencing databases for samples from patients with Crohn’s disease and rheumatoid arthritis, adding support to the molecular signaling pathway they defined.
“We think this response is a fundamental way that cells can sense heat and respond to stress,” Rathmell said. “Temperature varies across tissues and changes all the time, and we don’t really know what it does. If temperature changes shift the way cells are forced to do metabolism because of ETC1, that’s going to have a big impact. This is fundamental textbook kind of stuff.”
The findings suggest that heat can be mutagenic, when cells that respond with mitochondrial stress don’t properly repair the DNA damage or die.
“Chronic inflammation with sustained periods of elevated tissue temperatures could explain how some cells become tumorigenic,” Heintzman said, noting that up to 25% of cancers are linked to chronic inflammation.
“People ask me, ‘Is fever good or bad?’” Rathmell added. “The short answer is: A little bit of fever is good, but a lot of fever is bad. We already knew that, but now we have a mechanism for why it’s bad.”
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health
A multi-institutional clinical trial led by Weill Cornell Medicine and NewYork-Presbyterian investigators showed that a newer technique for collecting prostate biopsy samples reduced the risk of infection compared with traditional biopsy approaches and removed the need for prophylactic antibiotics. The results of the study appear in JAMA Oncology.
The technique, called transperineal prostate biopsy, collects prostate tissue via a needle through the skin of the perineum, the area between the rectum and the scrotum. The procedure, which uses local anesthesia to numb the area, allows physicians to bypass the traditional and more infection-prone route of collecting prostate biopsy tissue with a needle through the rectum.
The PReclude infection EVEnts with No prophylaxis Transperineal (PREVENT) trial, funded by the National Cancer Institute, part of the National Institutes of Health, was conducted at multiple sites, including NewYork-Presbyterian/Weill Cornell Medical Center, NewYork-Presbyterian Queens and NewYork-Presbyterian Brooklyn Methodist Hospital. The study found no infections among 382 men randomised to undergo the transperineal procedure compared with six infections affecting 1.6% of the 370 men randomised to undergo the traditional transrectal biopsy procedure. The lower infection rate is particularly remarkable because the men in the transrectal biopsy group received a targeted course of antibiotics designed to help reduce their infection risk, and the men in the transperineal group received no antibiotics.
“Transperineal biopsy should be the new standard of care for prostate biopsy,” said Dr Jim Hu, Professor of Urologic Oncology at Weill Cornell Medicine. “It was as effective as the traditional transrectal biopsy approach at detecting cancer, but without the risk of infection or the need for antibiotics.”
Prostate biopsies are an essential tool for detecting prostate cancer, and about 3 million people worldwide undergo the procedure each year. Dr Hu noted that physicians collect about 90% of these biopsies in the United States via a transrectal procedure. Yet studies have found that 5% to 7% of patients develop infections after biopsy, and 1% to 3% require hospitalisation for these complications, he said. To help prevent infections, physicians typically prescribe a prophylactic course of antibiotics before the procedure.
Dr. Hu noted that the investigators used a personalised approach to prophylactic antibiotics in the patients undergoing the transrectal biopsy procedure. Rather than giving the men a broad-spectrum antibiotic or multiple antibiotics, they matched the antibiotics to cultures obtained from the patient’s rectum during prostate exams before the procedure. This targeted antibiotic approach reduced the infection rate in those undergoing the traditional transrectal procedure substantially compared with the national infection rate for the procedure. Yet, they achieved a statistically significant reduction in infections in the transperineal group by eliminating infections altogether.
“Transperineal prostate biopsy makes a common diagnostic procedure safer for men,” said Dr Hu, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “It also eliminates the use of antibiotics, helping to reduce the emergence of antibiotic-resistant infections, a growing public health concern.”
Despite the promise of the new procedure, Dr. Hu acknowledged a few hurdles to making it more widely available to men in the United States. He explained that few physicians in the country have been trained in the perineal procedure. Additionally, he noted that US insurers pay the same amount for either procedure but the transperineal biopsy costs more and takes longer to perform, creating a financial disincentive for physicians to make the switch.
However, there is reason to think the status quo will change, Dr Hu said, noting the switch to transperineal prostate biopsies in Norway after a man died after a routine transrectal prostate biopsy. The change virtually eliminated biopsy-related infections and deaths in that country with the nationwide switch to transperineal biopsy, he said.
“There is a strong case to make the switch,” he said. “It will take time. But as more patients request the new procedure, we think it will become more widely available.”
Researchers found that an intravenous iron preparation, ferric carboxymaltose, works faster and better than an oral iron tablet taken by mouth for the treatment of anaemia, with comparable safety. The findings were published in Lancet Global Health.
Anaemia is a common cause of ill-health or death in mothers and their babies, especially in sub-Saharan Africa and South-East Asia where more than four out of ten pregnant women have the condition. A sizeable proportion of pregnant women in Nigeria proceed to giving birth while still anaemic despite taking iron tablet for prevention during pregnancy. Some reasons for this are that some women do not tolerate the tablets because of side effects like diarrhoea, nausea, or vomiting, or they forget to take the tablets. Available iron preparations given through drip in Nigeria like iron dextran have been associated with high risk of severe side effect, while iron sucrose needs repeat dosing. There is a need for an effective and safer alternative to overcome these problems.
A team of researchers in a recently concluded clinical trial, called the IVON TRIAL, tested ferric carboxymaltose, which is new in Nigeria and most of sub-Saharan Africa.
They compared the effectiveness and safety of this medicine with that of a popular tablet preparation, ferrous sulphate, which is currently being used to treat anaemia in Nigeria. They found that this new medicine given intravenously works faster and better for anaemia treatment than oral iron tablets; and it is as safe as the tablet.
The study enrolled 1056 pregnant women, aged 15–49 years, who were between five and seven-and-half months pregnant and had anaemia with haemoglobin measurement less than 10 g/dL.
“We used a web-based platform to assign them to treatment groups. Half of the women were treated with one dose of iron given in drip through the vein while half took iron tablets three times a day till they gave birth”, says Ochuwa A. Babah, a doctoral student at the Department of Global Public Health, Karolinska Institutet and one of the authors of the paper.
Their haemoglobin levels and iron levels were checked, and they were screened` for depression at specific time points. They were followed-up until six weeks after delivery to collect more data from mother and baby. Blood was collected from the baby’s cord at delivery to know if the medicine affected the baby’s phosphate level.
Works better for iron deficiency anaemia
Only one dose of iron (ferric carboxymaltose) given by drip through a vein during pregnancy causes a faster rise in blood level after four weeks compared to iron tablet taken by mouth three times every day. The drip iron also corrects low body iron better than iron tablets. The side effects of the drip iron are comparable to that with iron tablets, with no adverse effect on the babies.
“These findings are reassuring because pregnant women often reject new medicines because of fear of harm to their babies. We now have evidence that implementing the use of this new iron via drip (ferric carboxymaltose) in regions where many pregnant women suffer anaemia like Africa, will be a valuable step towards reducing the proportion of pregnant women who suffer from this condition and its complications”, says Ochuwa A. Babah and continues:
“The pregnant women were willing to accept iron via drip during pregnancy, supported by their families. The healthcare workers were ready to administer iron via drip but identified a need to increase staff strength and possibly medicine subsidy. We know from the clinical trial that the intravenous iron is effective and safe, so we are already liaising with the Federal Ministry of Health, Nigeria to add it to the essential drug list.”
A newly published study in the scientific journal Science Immunology has investigating how MAIT cells (mucosa-associated invariant T cells) behave in different tissues. The Karolinska Institutet study shows that these immune cells, which play an important role in the body’s defence against microbes, exhibit different properties depending on the tissue they are in.
MAIT cells are a type of T cell that recognise by-products formed when microbes synthesise riboflavin. This makes them unique in the way they detect and fight infections. The researchers examined MAIT cells from blood, barrier tissues and lymphoid tissue samples from organ donors to understand how these cells function in different tissues.
Different MAIT cells in intestines and liver
“We found that MAIT cells in the intestines have a specialised immunoregulatory profile with high expression of the regulatory enzyme CD39, suggesting that they play a role in protecting the intestinal barrier,” says Johan Sandberg, Professor at the Center for Infectious Medicine (CIM), at the Department of Medicine, Huddinge, Karolinska Institutet.
“In the liver, on the other hand, MAIT cells predominantly exhibit high expression of the marker CD56 and an increased ability to fight microbes.”
The study also shows that the number of MAIT cells in the blood decreases with age but is preserved in the tissues. At the same time, tissue-adapted functions in the intestines and liver become increasingly evident with age.
“Our results highlight the functional heterogeneity of MAIT cells and their adaptation to different tissues.”
The results of the study add a new dimension to the understanding of the immune system and how different types of immune cells specialise to protect different tissues against infections.
“This gives us a better understanding of how this arm of the immune system works and can help us develop new treatments for infectious diseases,” says Johan Sandberg.
South Africa has the third highest suicide rate in Africa and Africa has higher rates of suicide than any other continent. In the wake of World Suicide Prevention Day on September 10th, clinical psychologist Vincenzo Sinisi asks what can be done to bring down suicide rates.
Africa is currently the region with the highest suicide rate worldwide, according to the World Health Organization (WHO). This is driven by a combination of factors, including poverty, unemployment, and untreated mental health issues.
South Africa, with a suicide rate of 23.5 per 100 000 people, ranks third worst on the continent. South Africa is closely followed by Lesotho and Eswatini – countries where limited access to mental health services exacerbates the issue.
Age and gender impact suicide risk. In South Africa, for instance, suicide has been rated as the fourth leading cause of death among people aged 15 to 24, reflecting the devastating mental health toll on young people. The gender disparity is stark – men are four to five times more likely to die by suicide than women. However, women tend to report twice as many suicide attempts as men, indicating a significant gap in prevention efforts targeting both genders
Why is it happening?
While suicide is a global challenge, it manifests differently across Africa due to a variety of factors – these include economic hardship, mental health stigma, and the scarcity of healthcare resources.
Mental healthcare in Africa is severely underfunded. Many African countries have an insufficient number of mental health professionals – sometimes as few as one psychiatrist per 500 000 people. This is compounded by widespread mental health stigma, which prevents many people, particularly men, from seeking help. In some African cultures, suicide is stigmatised to the extent that it is linked to supernatural beliefs, such as curses or sorcery. These deep-seated cultural beliefs often lead to underreporting of suicide cases and contribute to delayed intervention.
In addition to cultural taboos, socioeconomic stressors like unemployment, poverty, and housing insecurity further drive suicide rates across the continent. In South Africa’s townships, the levels of indebtedness and joblessness create a cycle of despair that feeds into psychological distress, ultimately increasing the risk of suicide.
In South Africa, the impact of socioeconomic instability on mental health is evident, particularly in rural and impoverished urban areas. The link between unemployment and mental health distress is well-documented, and for many, this distress leads to thoughts of suicide. In economically deprived areas, suicide prevention efforts are often undermined by poor access to healthcare and low mental health literacy. As economic hardship worsens, so does the mental health of affected populations.
What to do?
Preventing suicide in South Africa and on the African continent more broadly requires a multi-level strategy, combining grassroots initiatives with government support. Many successful interventions have originated from community-based programmes tailored to local needs and cultural contexts – there are after all large differences between countries and, for example, between urban and rural areas.
As a starting point, community involvement is crucial in creating a supportive environment for those at risk. By training community leaders, including traditional healers and faith-based leaders, to recognise signs of mental health struggles, these communities can provide immediate support. Peer support networks have also proven effective, especially in areas with limited access to formal healthcare services. Such networks empower individuals to check in on one another and provide emotional support in times of crisis.
For example, the South African Depression and Anxiety Group (SADAG) runs mental health education programmes across rural South Africa, equipping local leaders and volunteers with tools to recognise and respond to signs of suicide. These efforts are helping to reduce stigma and encourage early intervention in communities often overlooked by national healthcare systems.
While community-led efforts are invaluable, government policy is essential for creating systemic change. South Africa’s National Mental Health Policy Framework (2023-2030) aimed to integrate mental health care into the primary healthcare system. Still, its implementation has been slow, particularly in rural areas. Expanding this framework and ensuring proper funding for mental health initiatives must be a priority. (Spotlight previously reported on expert responses to the new mental health policy.)
Governments can also collaborate with NGOs and the private sector to expand mental health services.
Telehealth and digital solutions have for example emerged as potential tools for addressing mental health challenges, particularly in areas where access to mental health professionals is limited. Telehealth services enable patients in remote and underserved areas to consult with mental health experts without travelling long distances. This is especially helpful for individuals who might otherwise be unable to access support due to geographic or financial barriers. One such initiative I am involved with is TherapyRoute.com, a platform that connects people with therapists and psychologists across Africa and that maintains a database of South African community health clinics.
Such a digital approach, though promising, still faces challenges. Internet access remains inconsistent in many parts of Africa, and telehealth services must continue to evolve to ensure they are accessible to most of the population. Increasing investment in digital infrastructure will be a critical part of expanding access to mental health services.
Practical strategies
Meanwhile, there are practical things we can do now. Suicide prevention is after all not the responsibility of healthcare professionals alone – everyone can contribute.
We can all be on the lookout for the warning signs. Sudden withdrawal from social activities, mood changes, declining self-care and hygiene, and expressions of hopelessness or helplessness (e.g., “I can’t go on” or “Everyone would be better off without me”) should never be ignored.
If someone you know appears to be at risk, ask direct questions about their mental health. Don’t be afraid to ask if they are considering suicide. Studies show that directly asking about suicide can reduce the risk of an attempt by giving the person a chance to talk about their feelings.
We can also respond as a community. We can organise peer support groups where people can check in on one another. Training community leaders, traditional healers, or local volunteers to recognise suicide risk and provide mental health first aid is another effective way to support those at risk. Running community-wide campaigns to raise awareness about mental health issues and reduce stigma can help normalize seeking professional help.
Governments also have a critical role to play. They must prioritise mental health by increasing funding for prevention and treatment programmes, particularly in rural and underserved areas. The success of such programmes depends heavily on their accessibility to people from all economic backgrounds.
In South Africa, government should focus on implementing the National Mental Health Policy Framework, ensuring it reaches the rural areas that are most in need. By integrating mental healthcare into primary healthcare services, as envisaged in the policy framework, more people will have the chance to receive timely care.
Ultimately, suicide prevention requires a multi-level approach, with involvement from individuals, communities, governments, and the private sector. By recognising warning signs, reducing mental health stigma, and expanding access to care through both in-person and telehealth services, we can make meaningful strides in reducing the suicide rate across Africa.
*Sinisi is a clinical psychologist and psychoanalyst in private practice in Cape Town. He is also a faculty member of the South African Psychoanalysis Association, The South African Psychoanalytical Initiative, and the Centre for Group Analytic Studies.
People in need of help can contact SADAG on the following helplines:
0800 21 22 23 (8am to 8pm)
0800 12 13 14 (8pm to 8am)
SMS: 31393
Also see this webpage for a longer list of helplines.
Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.
Republished from Spotlight under a Creative Commons licence.
Kidney and ureteral stones. Credit: Scientific Animations CC4.0
Sometimes all it takes is a little push. That is the conclusion of a study, published recently in the Journal of Urology, in which doctors used a handheld ultrasound device to nudge patients’ kidney-stone fragments.
As many as 50% of patients who have kidney stones removed surgically still have small fragments remaining in the kidneys afterward. Of those patients, about 25% find themselves returning for another operation within five years to remove the now-larger fragments.
UW Medicine researchers found, however, that patients who underwent the stone-moving ultrasound procedure had a 70% lower risk of such a recurrence.
“I think the main takeaways of this study are removing fragments reduces relapse and using a noninvasive, hand-held ultrasound device to help clear these kidney stone fragments,” said UW Medicine urologist Dr Jonathan Harper, the study’s senior author.
The multisite, randomised and controlled trial was conducted from May 2015 to April 2024. Almost all of the 82 participants were from the UW Medicine or the VA Puget Sound health systems. All had stone fragments that had persisted in their kidneys for months, and their ureters were free of stones and fragments.
In the study, 40 underwent ultrasound treatment to encourage fragments to clear from the kidneys, while 42 control-group members received no such treatment.
With patients awake in a clinic office setting, doctors used a wand that generated ultrasonic pulses through the skin to move the fragments closer to the ureter, where they could be naturally expelled, sometimes with the next urination, Harper noted.
Harper and his co-lead author on the paper, urologist Dr Mathew Sorensen, have worked on this technology and treatment for 15 years. They also use this technology, called burst wave lithotripsy, to blast larger stones into smaller pieces; those successes were published in 2022.
The pushing and breaking technologies are used with the same ultrasound platform.
Harper expressed hope that both clinical uses of the technology would become commonplace. A company, SonoMotion, is commercialising the technology, which was developed at the University of Washington, he added.
“I see a lot of potential in this It could become as common as getting your teeth cleaned. If you have a couple of small stones which could cause future problems, you make an office appointment and in 30 minutes you’re done.
“This could really revolutionise kidney stone treatment,” Harper said.
Human breast milk regulates a baby’s mix of microbes, known as the microbiome, during the infant’s first year of life, in turn lowers the child’s risk of developing asthma, according to a new study published in Cell.
Led by researchers at NYU Langone Health and the University of Manitoba, the study results showed that breastfeeding beyond three months supports the gradual maturation of the microbiome in the infant’s digestive system and nasal cavity, the upper part of the respiratory tract. Conversely, stopping breastfeeding earlier than three months disrupts the paced development of the microbiome and was linked to a higher risk of preschool asthma.
Some components in breast milk, such as complex sugars called human milk oligosaccharides, can only be broken down with the help of certain microbes. This provides a competitive advantage to microbes capable of digesting these sugars. By contrast, infants who are weaned earlier than three months from breast milk and who then rely solely on formula feeding, become home to a different set of microbes –ones that will help the infant to digest the components in formula. While many of these microbes that thrive on formula do eventually end up in all babies, the researchers showed that their early arrival is linked to an increased risk of asthma.
“Just as a pacemaker regulates the rhythm of the heart, breastfeeding and human milk set the pace and sequence for microbial colonisation in the infant’s gut and nasal cavity, ensuring that this process occurs in an orderly and timely manner,” said study co-senior investigator and computational biologist Liat Shenhav, PhD. “Healthy microbiome development is not only about having the right microbes. They also need to arrive in the right order at the right time,” said Dr Shenhav, an assistant professor at NYU Grossman School of Medicine, its Institute for Systems Genetics, and the school’s Department of Microbiology.
For the study, Dr Shenhav, who is also an assistant professor at NYU’s Courant Institute of Mathematical Sciences, worked in collaboration with study co-senior investigator Meghan Azad, PhD, director of the Manitoba Interdisciplinary Lactation Center, and a professor of paediatrics and child health, at the University of Manitoba.
Another key study finding was that the bacterium Ruminococcus gnavus appeared much sooner in the guts of children who were weaned early from breast milk than in those of children who were exclusively breastfed. The bacterium is known to be involved in the production of molecules called short-chain fatty acids, and the formation and breakdown of the amino acid tryptophan. Both tryptophan and its metabolites have been linked to immune system regulation and disruption in previous research, including an increased risk of asthma. The study authors noted that beyond aiding in digestion, an infant’s microbiome plays a crucial role in the immune system’s development.
The study tracked the ebb and flow of microbes in the guts and noses of infants during the first year of life, as well as details on breastfeeding and the composition of their mothers’ milk. All the children and their mothers were participating in the CHILD Cohort Study, a long-term research project that has been studying the same 3500 Canadian children at different stages of life from the womb well into adolescence.
The data provided by the CHILD Cohort Study enabled researchers to detangle the impact of breastfeeding on an infant’s microbiome from a range of other environmental factors, including prenatal smoke exposure, antibiotics, and the mother’s asthma history.
Even when these factors were accounted for, they found that breastfeeding duration remained a powerful determinant for the child’s microbial makeup over time. They also used these microbial dynamics and data on milk components to train a machine learning model that accurately predicted asthma years in advance. Finally, they created a statistical model to learn causal relationships, which showed that the primary way breastfeeding reduces asthma risk is through shaping the infant’s microbiome.
“The algorithms we developed provide valuable insights into microbial dynamics during an infant’s first year of life and how these microbes interacted with the infant,” said Dr Shenhav. “These insights allowed us to move beyond identifying associations, enhancing our ability to make predictions and explore causal relationships.
“Our research highlights the profound impact of breastfeeding on the infant microbiome and breastfeeding’s essential role in supporting respiratory health. By uncovering the mechanisms behind the protective effects of breast milk, as demonstrated in this study, we aim to inform national guidelines on breastfeeding and weaning from breast milk in a data-driven manner.
“With further research, our findings could also contribute to developing strategies to prevent asthma in children who cannot be breastfed for at least three months,” she added.
Researchers discovered a drug that safely and effectively helped cancer patients when they suffered from cachexia, a common condition related to cancer that involves weight loss and muscle wasting.
The results of the randomised phase 2 clinical trial, which included 187 individuals who experienced cachexia with pancreatic (32%), colorectal (29%) or non–small-cell lung (40%) cancer, appear in the New England Journal of Medicine. Richard Dunne, MD, MS, a Wilmot Cancer Institute oncologist and cachexia expert was part of the large group of investigators who ran the nationwide clinical trial.
Cachexia involves loss of appetite and weight, muscle-wasting, fatigue, and weakness. It affects more than 50% of people who have cancer, and currently there are no FDA-approved treatments.
Scientists discovered that the monoclonal antibody ponsegromab blocks a hormone known as GDF-15 that regulates appetite and body weight. The patients in the trial had elevated levels of GDF-15, a primary driver of cachexia, and ponsegromab improved many aspects of cachexia and its symptoms.
Patients were randomised to receive ponsegromab at doses of 100mg, 200mg, or 400 mg, or to receive placebo. At 12 weeks, patients in the ponsegromab groups had significantly greater weight gain than those in the placebo group, with a median between-group difference of 1.22 kg in the 100mg group, 1.92 in the 200mg group, and 2.81 in the 400mg group. Improvements were observed across measures of appetite and cachexia symptoms, along with physical activity, in the 400mg ponsegromab group relative to placebo.
Drugmaker Pfizer supported the study, and released this news. Side effects were minimal, Dunne said, and in fact ponsegromab appeared to be safer than common appetite stimulants used by cachexia patients.
“This is super exciting,” said Dunne, an associate professor of Medicine at the University of Rochester Medical Center. “This study is an important step in providing treatment for the hundreds of thousands of patients who suffer from poor quality of life due to cachexia.”
Several academic medical centres participated in the clinical research, which was led by John D. Groarke, MB, BCh, MPH, at Pfizer. Investigators are continuing to study GDF-15 and the importance of the biomarker in several types of cancer. Other clinical trials are also testing additional cachexia treatments that do not target the GDF-15 pathway.
Professor Glenda Gray, internationally known for her research in HIV vaccines and interventions to prevent transmission of HIV from mother to child, received the country’s highest honour, the Order of Mapungubwe, in 2013. (Photo: Biénne Huisman/Spotlight)
By Biénne Huisman
After a decade at the helm of the country’s primary health research funder, Professor Glenda Gray will focus again on doing the science. She tells Spotlight’s Biénne Huisman about her childhood, her passion for research, administering multi-million dollar grants, and a heated argument in the bathroom with an ANC bigwig.
Professor Glenda Gray, the first woman president and chief executive of South Africa’s Medical Research Council (SAMRC), has among others been described as outspoken, credible and tenacious. After a decade at the helm of the SAMRC, Gray retains her reputation for fearlessly speaking truth to power.
“Heading the SAMRC was definitely the best job of my life,” says Gray. “But I am excited about my future, it’s time for another best job. After ten years of doing science administration, it’s time to get back and do the science.”
Perhaps Gray’s fierce spirit was honed in her childhood, growing up in Boksburg on the East Rand, “on the wrong side of the tracks”. She laughs, remembering how American cable news channel ABC sub-titled her first TV interview, due to her strong “East Rand accent”.
Investing in research
From a childhood of counting cents, these days Gray administers multi-million dollar grants and passionately makes the case for greater investment in scientific research.
She says that while South Africa’s health department has competing priorities, ideally it should double or triple its allocation to research.
“We spend a lot of time trying to show the Department of Health how important science is. And so while there is commitment from them, they’re so busy worrying about services; healthcare workers, doctors, hospitals falling down, no equipment, no cancer treatment. And so, sometimes science is seen as esoteric and a luxury.”
Speaking to Spotlight during her lunch break at an SAMRC event in Cape Town, Gray adds: “Science gives you evidence to reduce morbidity and mortality. All the things that change people’s lives; like covid vaccines, ARVs, mother to child transmission interventions, typically these stem from research. And so, you can only improve outcomes if you fund research. Currently, the SAMRC gets around R750 million from government a year; in my view, around R2 to 3 billion a year is needed to really make profound investments in research.”
Supplementing the funding from the government, the SAMRC has scores of international funders and collaborators, such as the United States National Institutes for Health. One concern with such international donor funding is that local research may end up pandering to agendas set abroad.
Gray rejects this suggestion. “We [the SAMRC] always fund the ten most common causes of mortality and morbidity in South Africa. So the funders who work with us have to agree on funding what we deem our priorities.”
One of these priorities is transformation. “So I spent ten years of my life changing who we funded, where we funded, how we funded; changing the demographics of the SAMRC, creating an executive management committee that was diverse, and being able to attract a great black scientist [Professor Ntobeko Ntusi] to take over from me,” says Gray.
While having passed the public mantle onto Ntusi in July, the paediatrician and renowned HIV vaccinologist, named one of Time magazine’s 100 most influential people in 2017, will continue her HIV vaccine research. Gray is heading a major USAID funded study aimed at “galvanising African scientists, mostly women, into discovering and making an HIV vaccine.” She also holds tenure as a distinguished professor at the University of the Witwatersrand’s Infectious Diseases and Oncology Research Institute.
Give and take
Speaking to Spotlight, Gray reflects on managing the political side of the SAMRC – the intersection between politics and science: “As the president of the MRC, you have to be very brave and you have to be able to speak truth to power. Sometimes it’s hard, and sometimes it’s easy.”
This, she says, is a dance of give and take: “The relationship has to be flexible. Because, sometimes scientists are wrong and politicians are right. Sometimes politicians are wrong and scientists are right. And sometimes both are wrong, and sometimes both are right. And our egos can get in the way. You know: ‘Oh, you took me off the MAC [Ministerial Advisory Committee], now I’m not going to help you’. That’s not the right attitude to have…”
COVID-19 lockdown ruckus
Gray served on the Department of Health’s COVID-19 MAC at the height of the pandemic. In May 2020, she caused a ruckus for breaking away from the committee’s more measured counsel, turning to the press to criticise government’s lockdown regulations as “unscientific”.
She said the hard lockdown was causing unemployment and unnecessary hardship and malnourishment in poor families. Later as the hard lockdown started to lift, she spoke out against government’s continuation of restrictions on school going, the sale of certain foods and clothes like open-toe footwear, and the limits on outdoor exercise. “It’s almost as if someone is sucking regulations out of their thumb and implementing rubbish, quite frankly,” she told journalists at the time.
Then health minister Dr Zweli Mkhize rebuked Gray’s claims and sidelined her in the MAC before excluding her from a newly constituted MAC in September. The acting Director-General of Health, Anban Pillay, wrote to the SAMRC board urging them to investigate Gray’s conduct. As the fray deepened, the SAMRC board failed to back Gray. The council’s boardwas was acting in a “sycophantic manner aimed at political appeasement”, lamented a guest editorial published in the South African Medical Journal.
Despite this public falling-out, the following year, in February 2021, Gray worked with Mkhize to bring vaccines to South Africa’s healthcare workers.
“So basically at that stage government didn’t have a vaccine programme, and I bailed them out,” she tells Spotlight.
In February 2021, results from a clinical trial showed that the Oxford AstraZeneca COVID-19 vaccine – then intended for rollout in South Africa – performed poorly in preventing mild to moderate illness caused by the Beta variant of SARS-CoV-2, which was dominant at the time.
Gray says she was approached by Mkhize about an alternative vaccine – to which she responded by facilitating the procurement of 500 000 doses of the Johnson & Johnson vaccine through personal connections. These were officially rolled out to healthcare workers on February 17, when President Cyril Ramaphosa received his jab at the Khayelitsha District Hospital. Spotlight previously reported in more detail on the procurement of those first 500 000 doses.
“The vaccines arrived in Johannesburg at about midnight,” Gray recalls. “Then the plane with the president’s vaccine touched down in Cape Town at 12:20pm; and we had to rush it to Khayelitsha to have him vaccinated at one o’clock”.
A bathroom row with a minister
Gray is no stranger to fighting for policies and treatments based on scientific evidence. She recalls an altercation with former health minister Nkosazana Dlamini-Zuma in a bathroom at the presidential residence in Pretoria (Mahlamba Ndlopfu) in the late 1990s – the era of AIDS-denialism under then President Thabo Mbeki.
“Thabo Mbeki had a national AIDS plan and they were about to publish it. So there was a meeting; we were presenting, and we had data that mother to child transmission interventions were affordable, or that it was actually cheaper to give ARVs to a pregnant woman, than to treat a child who is HIV positive. But they kept on saying it was unaffordable, and that they wouldn’t be doing it. And then, when I saw Dlamini-Zuma in the bathroom, I got into a fight with her and said: ‘but it is affordable!’”
Early years in Boksburg
One of six children born to a “maverick father”, whip-smart but taken to getting involved in crazy schemes, and a mother who later in life became a Baptist minister, Gray says they grew up poor.
“My parents would often run out of money in the middle of the month, having to scrounge for food, borrow milk or buy on the book (credit arrangements). So I know what it’s like to be on the other side of privilege.”
Gray relays how neighbours would drop by at her childhood home to borrow cups of sugar, to spy on their family – as, during apartheid, her father would entertain friends of colour.
Gray matriculated from Boksburg High School in 1980. The next year she enrolled for medical school at Wits, working part-time to pay her way: “I worked at an ABC shoe store, Joshua Door, selling furniture, making Irish coffees at Ster Kinekor, waitressing…”
In 1993, as HIV exploded across the country; pregnant with her first child, Gray watched her own stomach expand while treating HIV-positive expectant mothers at Chris Hani Baragwanath Hospital. “In those days, there were no ARVs for children,” she recalls. “And so women had to navigate this joy of a new life, with the fact that death was looming over them.”
Today, Gray has three children and lives in Kenilworth in Cape Town.
Commenting on her reputation for standing up to pressure, she smiles. “My tongue has gotten me into trouble. How do I feel about that? I just want to make sure that as scientists we let politicians and society know the data and the evidence. I feel passionate about translating science, I feel passionate about evidence. I feel passionate about science changing the world.”
Adcock Ingram Critical Care, a leading manufacturer and supplier of hospital and critical care products in Southern Africa, is taking another step towards improving patient care in the region through a strategic alliance with Medline.
Medline is one of the world’s largest manufacturers and distributors of medical supplies and services, with annual global sales in excess of US$23 billion. The partnership solidifies Adcock Ingram Critical Care as the exclusive distributor of Medline’s products in Southern Africa and is a testament to its commitment to provide quality products that improve the health and lives of people in the markets they serve.
Ranked as one of Forbes largest private companies, Medline delivers world-class products, robust supply chain resources and clinical practice expertise to clients in more than 125 countries. Medline’s innovative and cutting-edge MedTech portfolio includes more than 550 000 products, serving the entire continuum of care. Its extensive reach and product range have transformed healthcare delivery worldwide, making it a key player in driving efficiency and improving patient outcomes.
By partnering with Adcock Ingram Critical Care, Medline is bringing its global expertise to South Africa, strengthening the country’s healthcare infrastructure at a time when it is most needed.
“This is another milestone in our commitment to ensure that every South African can access the care they deserve. Together with Medline, we can help to build a stronger, healthier South Africa,” says Colin Sheen, Managing Director, Adcock Ingram Critical Care.
A Strategic Alliance with National Impact
For decades, Adcock Ingram Critical Care has been delivering essential medical solutions to the nation, from Medicine Delivery in Hospital Care to Renal Care, Transfusion Therapies, Infusion Systems and most recently Wound & Stoma Care. The strategic alliance with Medline will ensure expanded and continued medical access and support healthcare providers and patients across South Africa and Southern Africa.
“The Strategic Alliance with Medline is a significant milestone for us,” says Sheen. “This partnership will provide medical professionals across the country with access to world-class medical supplies and technology, empowering them to deliver better care and improved patient outcomes.”
Beyond its business scope and as part of its larger mission, Adcock Ingram Critical Care is connecting global medical innovations with local requirements, ensuring that hospitals, clinics, and healthcare providers – even in the most remote areas – have access to the essential tools needed to save lives.
“Adcock Ingram Critical Care’s knowledge of the South African medical sector, combined with Medline’s world-class products, creates a powerful synergy,” says Salam Hadla, Medline’s Vice President for the Middle East & Africa Region. “We are excited to partner with Adcock Ingram Critical Care to help advance care standards across Southern Africa. Our shared mission is to offer healthcare providers the highest quality products, ensuring better clinical outcomes and contributing to a stronger medical care system.”
Improving Healthcare for a Stronger Nation
South Africa is one of the largest medical technology markets in Africa and the Middle East, valued at over R21 billion in 2021 and projected to grow to R29.6 billion by 2025. As the demand for access to quality healthcare services increases, strategic alliances like Adcock Ingram Critical Care and Medline are vital in ensuring that healthcare providers are equipped at providing medical services and improving access in both urban and rural clinical settings.
