A new study led by the University of Southampton has found that medications for ADHD have overall small effects on blood pressure and heart rate after weeks or a few months of use.
There have been concerns about the side effects of ADHD medications but the new findings, coupled with other studies, suggest that the benefits of taking these medications outweigh the risks, while highlighting the need for careful monitoring.
The study, published in The Lancet Psychiatry, conducted the largest and most comprehensive analysis of the cardiovascular effects of ADHD medications based on the results of randomised controlled trials – the most rigorous type of clinical study to assess medication effects.
Professor Samuele Cortese, senior lead author of the study from the University of Southampton said: “When it comes to taking any medication, risks and benefits should always be assessed together. We found an overall small increase in blood pressure and pulse for the majority of children taking ADHD medications.
“Other studies show clear benefits in terms of reductions in mortality risk and improvement in academic functions, as well as a small increased risk of hypertension, but not other cardiovascular diseases. Overall, the risk-benefit ratio is reassuring for people taking ADHD medications.”
The study was funded by the National Institute for Health and Care Research (NIHR), within the framework of the NIHR Research Professorships scheme to Professor Samuele Cortese, with Dr Luis Farhat (University of São Paulo, Brazil) as first author and Professor Alexis Revet (University of Toulouse, France) as co-senior author.
It is estimated that attention-deficit/hyperactivity disorder (ADHD) affects around 4 per cent of children in the UK. Of these, around 45 per cent are treated with medication.
The international team of investigators analysed data from 102 randomized controlled trials, including a total of 22,702 participants with ADHD. They used an advanced statistical approach – network meta-analysis – that allowed them to compare the effects of several medications, even when the medications were not directly compared in the trials included in the analysis.
They found that all ADHD medications were generally associated with overall small effects on blood pressure, heart rate, and ECG parameters. With the exception of guanfacine (which leads to decreased blood pressure and heart rate), other medications led to increases in the values of these parameters.
No significant differences were found between stimulants (including methylphenidate and amphetamine) and non-stimulants (atomoxetine and viloxazine) with regard to their effects on blood pressure and heart rate.
“Our findings should inform future clinical guidelines, stressing the need to systematically monitor blood pressure and heart rate, both for stimulants and non-stimulants. This should be particularly relevant for practitioners who might assume that only stimulants have a negative effect on the cardiovascular system,” said Dr Farhat.
The researchers say that those with existing heart conditions should discuss the side effects of ADHD medications with a specialist cardiologist before starting treatment.
Professor Revet added: “Our findings, based on randomised controlled trials that tend to be of short duration due to ethical issues, should be complemented by results from real-world, longer-term studies.”
The research team will now look to see if some groups might be more vulnerable to cardiovascular side effects than others.
NIHR Research Professor Cortese concluded: “While our findings are informative at the group level, that is, on average, we cannot exclude that a subgroup of individuals may have a higher risk of more substantial cardiovascular alterations.
“While it is currently not possible to identify those individuals at higher risk, efforts based on precision medicine approaches will hopefully provide important insights in the future.”
A collection of immune cells known as a granuloma that results from chronic inflammation in the interstitial lung disease sarcoidosis. White dots indicate the receptor NRP2, which is overexpressed in response to inflammation. Credit: Scripps Research
Pulmonary sarcoidosis is a lung disease characterised by granulomas—tiny clumps of immune cells that form in response to inflammation. It’s the most inflammatory of the interstitial lung diseases (ILDs), a family of conditions that all involve some level of inflammation and fibrosis, or scarring, of the lungs. In the U.S., pulmonary sarcoidosis affects around 200 000 patients. The cause is unknown, and no new treatments have been introduced in the past 70 years.
In a paper published in Science Translational Medicine, scientists at Scripps Research and aTyr Pharma characterised a protein, HARSWHEP, that can soothe the inflammation associated with sarcoidosis by regulating white blood cells. Reducing inflammation slows the disease’s progression and results in less scarring. A phase 1b/2a clinical trial of efzofitimod, a therapeutic form of HARSWHEP, showed promising results.
“Taken together, these results validate a new way to approach immune regulation in chronic lung disease,” says Paul Schimmel, professor of molecular medicine and chemistry at Scripps Research and the study’s senior author.
The drug’s power lies in its gentle nature. “It’s not a hammer; it’s not overly suppressing the immune system. It’s just nudging the immune system in a certain way,” explains Leslie A. Nangle, Vice President of Research at aTyr Pharma and the paper’s first author. “And if you can quiet the inflammation, you can stop the cycle of ongoing fibrosis.”
HARSWHEP is part of an ancient class of proteins known as aminoacyl-tRNA synthetases (aaRSs). Typically, aaRSs play a key role in protein synthesis. “They’re in every cell in your body. They’re in every organism on the planet,” Nangle says. Over time, new versions known as splice variants have emerged that bind to receptors on the outsides of cells and initiate different events throughout the body.
One such variant, HARSWHEP, entered the picture about 525 million years ago. Nangle and Schimmel screened more than 4,500 receptors and were surprised to find that HARSWHEP will bind only to the receptor neuropilin-2 (NRP2). This receptor is known for its role in development of the lymphatic system—the circulatory system through which immune cells travel—not immune function. But the researchers found that when small, circulating white blood cells known as monocytes enter a tissue in response to inflammation and develop into larger, more specialized white blood cells known as macrophages, those cells start to express high levels of NRP2.
“We had a protein with an unknown function. We had a receptor that was doing something on immune cells that had never been characterized. So we had a couple things we had to match up,” Nangle says.
The team found that HARSWHEP binding to NRP2 physically transforms the macrophage. “It’s creating a new type of macrophage that is less inflammatory and actually helps to resolve inflammation,” Nangle explains.
To characterise HARSWHEP’s mechanism of action, the team administered the protein in mice and rats and found that it reduced lung inflammation and the progression of fibrosis.
In separately published clinical trial data, the team saw a positive impact on patients who were treated with efzofitimod while tapering off of oral corticosteroids. Long-term steroid treatment, currently the first-line option, is associated with significant weight gain and organ damage, and the immunosuppressive effects leave patients vulnerable to infection.
The team also characterised patients’ circulating immune cells before and after efzofitimod treatment. They saw that it reduced key indicators of the inflammation that drives sarcoidosis, such as the concentration of macrophages and other inflammatory immune cells.
While they’re exploring sarcoidosis first, efzofitimod is a potential treatment for many interstitial lung diseases, Nangle explains. The aTyr team plans to explore treating other ILDs and is running a clinical trial now for scleroderma-related ILD.
The work highlights macrophages as a possible target for treating ILDs, and the promise of HARSWHEP could foretell other aaRSs’ therapeutic potential.
Nangle describes this work as moving “from concept to clinic.” Schimmel has worked on aaRSs throughout his tenure at Scripps Research. aTyr Pharma spun out of Schimmel’s lab; his former graduate student Nangle was the company’s first employee upon opening their labs in 2006.
“Original work that happened at Scripps gave rise to the idea that this could be a new class of therapeutic molecules, Nangle says. “We have now moved it all the way to clinical development. It’s a proof of concept for this whole class of molecules and the work Paul has done.”
Dr Yvonne Holt, Chief Medical Officer of Next Biosciences (left) with Kim Hulett, Founder and CEO of the company (right) celebrating 20 years of innovation and leadership in stem cell banking, genetic testing and regenerative medicine.
As Next Biosciences celebrates its 20th anniversary, the pioneering South African biotech company reflects on two decades of significant advancements in science and healthcare.
From its roots in medical innovation to its transformative contributions in regenerative medicine, genetic testing and wellness, Next Biosciences has not only shaped the local industry, but also positioned itself as a leader in Africa’s growing biotech sector.
Founded by Kim Hulett, an entrepreneur with a background in finance and technology, and Dr Yvonne Holt, the company has expanded its range of products and services that cover biologics, stem cells, exosomes, genetic testing, longevity and reproductive health.
“The journey of Next Biosciences has been about bringing cutting-edge science and technology to South Africa, and making advancements in health and wellness accessible,” says Dr Holt, Chief Medical Officer at the company. “Every innovation we develop is driven by our mission to positively impact people’s health with science, by transforming lives, improving health outcomes and shaping the future of medicine on the continent.”
With a team of 90, Next Biosciences stands as one of the country’s leading biotech innovators. Women make up 80% of the workforce, with 20% of them being scientists – underscoring the company’s strong commitment to diversity and inclusion. Their lab is accredited by the Association for the Advancement of Blood and Biotherapies (AABB) and ISO 13485 standards, a testament to their excellence in stem cell banking, cord blood services and other biotechnological advancements.
From its beginnings with Netcare, Next Biosciences’ focus on research and development has enabled the company to expand beyond local borders, bringing its innovative healthcare solutions to a wider audience. They now lead initiatives that support regenerative medicine with products like OptiSerum, a revolutionary umbilical cord blood serum for ophthalmic use, and AmnioMatrix, used in a range of medical applications from ophthalmology and wound care to dentistry.
Next Biosciences’ state-of-the-art Netcells storage lab, ensuring the safe preservation of precious stem cells for future medical advancements.
“Biotechnology and regenerative medicine are advancing at an unprecedented pace, offering new possibilities for treating diseases that were once thought incurable. Our focus remains on harnessing these innovations responsibly, ensuring that the latest advancements in cellular therapies, genetic diagnostics and biologics translate into real, life-changing solutions for patients,” says Dr Holt.
The biotechnology landscape has evolved worldwide, and South Africa has not been left behind.
Credit: Global Biotech Indus
The global biotechnology industry is currently valued at $546 billion, growing at approximately 13% per annum. Remarkable advancements have been achieved in genetic research, stem cell therapies and personalised medicine. “The potential for biotechnology over the next decade is extraordinary,” says Hulett, CEO of Next Biosciences. Breakthroughs in regenerative medicine and longevity science are revolutionising healthcare as we know it.”
Next Biosciences’ path hasn’t been without challenges. From navigating regulatory hurdles to sourcing cutting-edge technologies, the company’s growth has been driven by passion, resilience and innovation. As a majority female-led team, the company exemplifies the power of women in science and business, and they have become a beacon for female entrepreneurs looking to make a mark in the science and technology sectors.
“Building a biotech company in SA, with all its complexities, required tenacity and a relentless commitment to our mission. Over the years, we have witnessed our industry evolve and we are proud to have been at the forefront of that change,” says Hulett. “The future holds great promise and we are excited to see what the next 20 years will bring.”
Looking ahead, Next Biosciences aims to expand its footprint in Africa, focusing on reproductive, regenerative and longevity health to empower individuals to invest in their health and live their best lives. With a strong commitment to innovation, accessibility, convenience and sustainability, Next Biosciences plans to integrate cutting-edge biotechnologies, while maintaining a patient-centric approach. By staying at the forefront of the biotech industry, the company is set to strengthen its position as a trusted leader in African healthcare.
Mass General Brigham investigators have linked difficult early life experiences with reduced quality and quantity of the white matter communication highways throughout the adolescent brain. This reduced connectivity is also associated with lower performance on cognitive tasks. However, certain social resiliency factors like neighbourhood cohesion and positive parenting may have a protective effect. Results are published in Proceedings of the National Academy of Sciences (PNAS).
White matter are the communication highways that allow the brain networks to carry out the necessary functions for cognition and behaviour. They develop over the course of childhood, and childhood experiences may drive individual differences in how white matter matures. Lead author Sofia Carozza, PhD, and senior author Amar Dhand, MD, PhD, of the Department of Neurology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, wanted to understand what role this process plays in cognition once children reach adolescence.
“The aspects of white matter that show a relationship with our early life environment are much more pervasive throughout the brain than we’d thought. Instead of being just one or two tracts that are important for cognition, the whole brain is related to the adversities that someone might experience early in life,” said Carozza.
The team studied data from 9082 children (about half of them girls, with an average age of 9.5) collected in the Adolescent Brain Cognitive Development (ABCD) study. This study, funded by the National Institutes of Health and conducted at 21 centres across the U.S., gathered information on brain activity and structure, cognitive abilities, environment, mood and mental health. The researchers looked at several categories of early environmental factors, including prenatal risk factors, interpersonal adversity, household economic deprivation, neighbourhood adversity, and social resiliency factors.
Carozza and Dhand used diffusion imaging scanning of the brain to measure fractional anisotropy (FA)—a way of estimating the integrity of the white matter connections—and streamline count, an estimate of their strength. They then used a computational model to compare how these features of white matter were related to both childhood environmental factors and current cognitive abilities such as language skills and mental arithmetic.
Their analysis revealed widespread differences in white matter connections throughout the brain depending on the children’s early-life environments. In particular, the researchers found lower quality of white matter connections in parts of the brain tied to mental arithmetic and receptive language. These white matter differences accounted for some of the relationship between adverse life experiences in early childhood and lower cognitive performance in adolescence.
“We are all embedded in an environment, and features of that environment such as our relationships, home life, neighbourhood, or material circumstances can shape how our brains and bodies grow, which in turn affects what we can do with them,” said Carozza. “We should work to make sure that more people can have those stable, healthy home lives that the brain expects, especially in childhood.”
The researchers note that their study is based on observational data, which means they cannot draw strong causal conclusions. Brain imaging was also only available at a single timepoint, offering a snapshot but not allowing researchers to track changes over time. Prospective studies—following children over time and collecting brain imaging information at multiple time points—would be needed to more definitively connect adversity and cognitive performance.
Scanning electron micrograph of a T cell lymphocyte. Credit: NIH / NIAID
When an infection is prolonged and severe, T cell exhaustion comes into play to prevent to reign in the immune system and prevent damage to the body. A study published in Nature reveals that right from the beginning of mild illness, the body also produces these special T cells previously known only from chronic, severe infections and tumours.
There are different types of T cells in the body, all of which play a crucial role in the immune system. They fight pathogens and control the immune response. However, some subtypes become less effective or even cease their activity altogether as the disease progresses. This has a protective function: in persisting infections, it would harm the body if the immune system continued to fight the pathogens aggressively. But in cancer treatment, T cell exhaustion means that therapeutic measures may no longer be effective.
Until now, it was assumed that the body only produces such T cells in severe and persisting infections. The results of the researchers, from Helmholtz Munich and the Technical University of Munich, show that this is not the case. “We were able to show that the body prepares T cell subtypes that are predisposed to exhaustion even in early infection phases of moderate diseases,” says Dietmar Zehn, Professor of Animal Physiology and Immunology at TUM and last study author.
Different T Cells for Different Purposes
The team deduces from the discovery that the body assembles a range of different T cells early on at the onset of the disease to arm itself for different disease progressions. Depending on the course of the disease, it then has cells at its disposal to make the immune response more aggressive or more gentle — and in some circumstances, even to abort it.
“Our results expand the classic idea of the development of T cell exhaustion,” says Dietmar Zehn. “We therefore assume that our observations will help to further decipher the mechanisms behind T cell exhaustion.” A better understanding of these processes could help in the future to control the immune response in a targeted manner — for example, to strengthen the immune system in cancer patients or to weaken excessive defences, as is typical in severe cases of COVID-19, for instance.
Although a woman’s ovaries produce the most oestrogen, various types of oestrogen are also synthesised throughout different tissues in the body, including the brain’s neurons. New research in The FEBS Journal indicates that such neuro-oestrogens help suppress appetite.
Knowing that the enzyme aromatase is important for the production of oestrogens, investigators depleted or knocked out the gene encoding aromatase in mice, so that the animals were unable to synthesise oestrogens in a systemic or body-wide manner. These mice demonstrated increased food intake and body weight compared with their aromatase-expressing counterparts. Restoring aromatase expression specifically in the brain reduced food intake and increased sensitivity to leptin, the “fullness” hormone, confirming that neuro-oestrogens can influence appetite.
To further investigate the role of neuro-oestrogens independently of ovarian oestrogen involvement, the researchers removed the ovaries in female mice. The brain’s hypothalamus (the central hub for appetite signals) in ovariectomised mice showed increased expression of the gene encoding aromatase, and these mice decreased their food intake.
“Our results imply that neuro-oestrogens likely contribute to appetite regulation and may be relevant for body weight reduction” the authors wrote.
Whether it’s an early morning jog, or a touch of Tai Chi, groundbreaking research from the University of South Australia shows that any form of exercise can significantly boost brain function and memory across children, adults, and older adults.
In the largest, most comprehensive umbrella review to date, researchers found that regular exercise improves general cognition, memory, and executive function in both healthy individuals and those with clinical conditions, reinforcing exercise as an essential, inclusive activity for optimising cognitive health. The review appears in the British Journal of Sports Medicine.
Synthesising findings from 133 systematic reviews, covering 2724 randomised controlled trials and 258 279 participants, the systematic umbrella and meta-meta-analysis found that:
low- to moderate-intensity exercise had the greatest benefits for brain function and memory
children and adolescents showed the greatest improvements in memory, while people with ADHD saw the biggest gains in executive function
yoga, Tai Chi, and exergames (active video games) delivered the most significant cognitive benefits.
Lead researcher, UniSA’s Dr Ben Singh, says the findings provide a comprehensive understanding of how different types, intensities, and durations of exercise influence cognitive function.
“Exercise has a profound effect on physical health, but we also know it benefits brain function. What this study confirms is that even low-intensity exercise – like yoga or walking – can improve cognition, making it accessible to people of all ages and abilities,” Dr Singh says.
“In particular, we found that benefits were delivered quickly – with clear gains within 1-3 months, highlighting that even small bursts of activity can make a big difference. It also signals that trying out new activities could play a key role in keeping the brain engaged and active.
“For children and teens, exercise was especially beneficial for developing memory, while for people with ADHD, it helped improve focus, reduce impulsivity, and enhance executive function.
“We also found that mind-body exercises, like Tai Chi and yoga, had the most significant impact on memory, while exergames – such as Pokémon Go – were highly effective for general cognition. This is an encouraging finding, as it suggests that engaging, low-impact activities can offer real cognitive benefits.”
Senior researcher, Professor Carol Maher says exercise should be encouraged as a cognitive health strategy across all ages and fitness levels.
“This study presents compelling evidence that exercise should be integrated into healthcare and education settings to promote cognitive well-being.
“Knowing that even small amounts of exercise can improve memory and brain function – especially for those at higher risk – presents a clear opportunity for exercise to be included in clinical and public health guidelines.”
Whooping cough, or pertussis, was once a leading cause of death for children worldwide before the introduction of vaccines in the 1940s. In the decades since, the bacterial disease was nearly eradicated in the U.S., with fatalities falling to double digits each year.
But the disease has made a troubling comeback in recent years as vaccine coverage declined after the COVID-19 pandemic. In 2024, several outbreaks left public health officials and hospitals scrambling to accommodate a sudden influx of patients, primarily infants, who are often too young to be vaccinated and suffer the most severe symptoms.
Now, new research from The University of Texas at Austin could aid in improving whooping cough vaccines to once again push this disease toward eradication by targeting two key weaknesses in the infection.
A New Target
Against this backdrop, a team of researchers, including members of UT’s McKetta Department of Chemical Engineering and Department of Molecular Biosciences, has made significant strides in understanding and enhancing pertussis immunity. One of the things that makes pertussis infections dangerous is pertussis toxin (PT), a chemical weapon produced by the bacteria that weakens a patient’s immune response and causes many of the severe symptoms associated with whooping cough.
The new research, described in a new study published in the Proceedings of the National Academy of Sciences, focuses on two powerful antibodies, hu11E6 and hu1B7, which neutralise the PT in different ways.
Using cutting-edge cryo-electron microscopy approaches, the researchers identified the specific epitopes on PT where these antibodies bind. Epitopes are chemical targets the immune system can zero in on to fight pathogens. Hu11E6 blocks the toxin from attaching to human cells by interfering with sugar-binding sites, while hu1B7 prevents the toxin from entering cells and causing harm. These findings are the first to precisely map these critical regions, providing a blueprint to improve vaccines.
“There are currently several promising new pertussis vaccines in the research and clinical trial phases,” said Jennifer Maynard, professor of chemical engineering at the Cockrell School of Engineering and corresponding author of the new study. “Our findings could be incorporated into future versions quite easily, improving overall effectiveness and longevity of protection.”
She pointed to innovations like mRNA technology used in the COVID-19 vaccine, as well as breakthroughs in using genetic engineering on pertussis toxin (PTgen) to generate safer and more potent new recombinant acellular pertussis vaccines as technologies preserving neutralizing epitopes that can combine with her team’s new findings.
“Training the immune system to target the most vulnerable sites on the toxin is expected to create more effective vaccines,” Maynard said. “And the more effective and longer-lasting a vaccine is, hopefully, the more people will take it.”
In addition to helping guide future vaccine designs, the hu1B7 and hu11E6 antibodies themselves hold promise as therapeutic medicines for infected and high-risk infants. Previous work by Maynard and colleagues show that they can prevent the lethal aspects of pertussis infection. UT researchers are actively seeking partnerships to develop ways to prevent lung damage and death in newborns exposed to the disease.
A Persistent Threat
Caused by the bacterium Bordetella pertussis, whooping cough is infamous for its violent coughing fits, which can lead to complications like pneumonia, seizures, and even death, particularly in infants. One nickname for the disease is the 100-days cough because the painful coughing fits can linger for months, even in mild or moderate cases. The disease kills an estimated 200 000 people each year worldwide, most of them infants and children, and survivors of severe illness can be left with brain damage and lung scarring.
While modern vaccines have reduced the toll, their effectiveness wanes over time, with protection only lasting two to five years. Modern pertussis vaccines are acellular, which means they contain portions of the bacteria that train the immune system to recognize the pathogen, including PT.
Recent outbreaks of whooping cough around the world have stunned public health officials. This fall, New York City saw a 169% increase in whooping cough cases since 2023. Cases have increased 500% since 2019. Australia is currently suffering through the largest outbreak of whooping cough since the introduction of the vaccine in the 1940s, with an estimated 41,000 cases reported this year.
Health officials point to missed initial and booster vaccinations as major contributors to the outbreaks.
Overcoming Hesitancy
While advances in fighting pertussis are exciting, they face a dual challenge: overcoming the biological complexity of pertussis and the societal hurdles of vaccine hesitancy. The most effective way to prevent pertussis in vulnerable newborns is for mothers to be vaccinated during pregnancy, which confers protection to the newborn until it is old enough to be vaccinated. According to the CDC, the full vaccination rate against pertussis in kindergarteners is typically over 90% in the US, but under 60% of mothers receive the vaccine during pregnancy. Skepticism about vaccine safety and slow normalization of routine vaccination after the COVID-19 pandemic has led to pockets of under-vaccinated communities and overall low protection of newborns, providing fertile ground for deadly outbreaks. This environment, coupled with the limitations of current vaccines, makes innovation essential.
Co-author Annalee W. Nguyen, a research professor in chemical engineering, emphasized the importance of prevention over treatment. “It’s always easier to prevent disease in a high-risk person,” she said. “Once someone is extremely ill, their immune system isn’t functioning well, and it’s harder to help them recover. Mothers have an incredible opportunity to shield their babies after they are born by getting a pertussis booster vaccination during pregnancy, and parents can continue to protect their families by working with their pediatrician to ensure children and teens are up-to-date on vaccinations.”
By focusing on neutralizing epitopes—areas where antibodies can effectively block the toxin—new vaccines can potentially provide stronger, longer-lasting immunity. This could help bolster public confidence in pertussis vaccines and curb the disease’s resurgence.
For centuries, it was believed that tuberculosis spread primarily when a vulnerable person spends hours in a poorly ventilated space with someone infectious. But new findings suggest that much TB transmission also occurs through casual contact.
Conventional thinking held that enclosed spaces such as households, prisons, and shelters, where people spent long periods of time together, were where most TB transmission took place. But new data suggest that casual contact at social settings like shopping malls, restaurants, bars, and places of worship also account for much TB transmission.
A recent study found that close contact explained only 9% of TB transmission links, while casual contact accounted for 49%. The study, called CONTEXT (Casual Contact and Migration in XDR TB), was conducted in KwaZulu-Natal.
The study’s lead author, Professor Neel Gandhi of Emory University in Atlanta, recently presented the findings at the Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco. The work has not yet been published in a peer-reviewed medical journal.
The new findings come in the context of other research (much of which was conducted in Cape Town) that suggest TB could be transmitted through breathing, and growing evidence that people with asymptomatic TB can transmit the infection.
Where transmission occurs
Gandhi tells Spotlight that TB transmission has traditionally been linked to prolonged, close contact, with previous studies showing that 9 to 30% of cases could be attributed to this type of contact. A compelling alternative argument, he says, is that the remaining 70% of transmission occurs due to casual contact in community settings – which is what their research sought to explore.
He elaborates: “For much of history, we have thought that most TB transmission occurs through close and prolonged contact, meaning that a susceptible person is spending a lot of time in a poorly ventilated area with somebody who is infectious. And so most often we think of households as places where transmission occurs; or congregate settings, places like prisons or homeless shelters.”
On defining casual contact, he says: “In our research, we wanted to understand less intense forms of contact where transmission can occur. So, we understood where people lived, but we also asked them where they spent time in a typical week. The phrase we used was: ‘where do you spend two hours or more, most weeks?’ To try to identify the places people spend substantial amounts of time; and seeing whether they crossed paths with somebody else to whom their molecular fingerprints (of their TB bacteria infection) match.”
Genotyping, and geomapping
In their study, Gandhi and his colleagues made use of both genotyping and geospatial mapping to figure out where TB transmission likely occurred.
Genotyping, explains Gandhi, is a technology developed about 30 years ago that allows us to examine the genetic code of TB bacteria, and to compare similarity between patients’ bacteria.
“TB is a bacteria that keeps its genetic code similar across many generations of replication. In layman’s terms, we call this molecular fingerprinting. If I were to transmit TB to somebody else; my TB bacteria and that person’s TB bacteria’s genetic codes would look very similar – almost identical – so we could use this fingerprinting technique by sequencing the genomes of the two TB bacteria to try to fully get a sense of what the likelihood of transmission was.”
Commenting on their geospatial methodology, he says: “When our participants told us where they live or where they spend time in the community, or where they get outpatient healthcare; our team went to those sites and captured a GPS coordinates.
“Just like we use GPS for mapping when we’re trying to get around town, we would get specific coordinates… If two people went to the same shop, they might have used different names for that shop, or let’s say they went to a shopping mall, they may have used different names for those places; but we used GPS coordinates allowing us to determine whether they were at the same place or close to one another. And we used the concept of proximity to try to understand the likelihood that they may have crossed paths.”
In the study they used the metric of “community proximity” defined as a radius of 500 metres, or less.
Gandhi illustrates the nuance of geomapping, using his university campus: “So the example I like to give is; I work in a building called the School of Public Health. Across the courtyard is the School of Nursing. If you just asked me, where do you work? I would tell you, I work in this building. If you ask the next person where they work, they may say, I work in the School of Nursing. That wouldn’t match up in terms of place name. But if we used a radius of 100 metres or 500 metres, we can determine that we work very close to one another. And there’s a cafe in yet another building that we may have eaten lunch in at the same time. TB being an airborne disease, I don’t have to sit next to that person or even to know that person; if I’m infectious, I could have transmitted to them if they were sitting and eating in the same room.”
Essentially, the researchers used genotyping, particularly molecular fingerprinting to help understand the likelihood of transmission between people who have drug resistant TB. And once individuals with similar molecular fingerprints were found, they used geomapping to see whether these patients could be connected through close contact – and if not close contact, then through casual contact.
He adds: “The most common place people told us were friends and family members’ homes. Then the next most common was places of shopping so shopping malls.”
At CROI, Gandhi responded to a question from a conference delegate around risk, saying that there appears to be a greater risk of TB transmission in social settings than previously understood.
Symptoms and disease
To Spotlight, he says more work is needed to understand why casual contact transmission is happening. “And it connects to another topic in the TB community that is gaining a lot of attention currently, which is trying to understand what the association is between symptoms and having TB disease,” says Gandhi.
He notes that the challenge for researchers moving forward is understanding the link between infectiousness and symptoms – specifically, understanding when a person becomes infectious, even if they show no symptoms.
Most TB public health interventions are still based on the assumption that people with TB will present at health facilities with classic TB symptoms such as persistent cough, night sweats, fever, weight loss, and chest pain. South Africa has however in recent years been offering TB tests to asymptomatic people thought to be at high risk of TB, as part of its targeted universal testing strategy.
“So you may have heard of this concept of what some people have called subclinical TB or asymptomatic TB. And that is to say, if you were to test a group of people who didn’t come to a health clinic, but let’s say you were on a street corner and you tested everybody who went by for TB, we’re coming to appreciate that as many as 50% of people may not either have any symptoms or may not have symptoms that are worrisome enough for them to seek healthcare, but are actually testing positive for TB disease,” Gandhi adds.
Gandhi says this reminds him of the early days of COVID-19, when scientists weren’t sure if people only became infectious after showing symptoms.
“Eventually we learned that people were infectious probably for a few days before they developed symptoms. And in the TB world, this may be an area we need to investigate. If there’s the possibility that somebody is infectious when they have absolutely no symptoms, they would go about their regular activities; going to work, going to school, going shopping, going to religious ceremonies, going to restaurants, and they may unknowingly be infectious with TB. So this is the challenge.”
The bigger picture
Commenting on the findings, Robert Wilkinson, Honorary Professor in the Department of Medicine at the University of Cape Town and director of the Centre for Infectious Diseases Research in Africa, says: “It is interesting, and the proportion of transmission estimated to occur outside the household is a low estimate, but not incompatible with other estimates.”
He notes that the phenomenon of transmission occurring after brief casual contact is not novel though, and has been investigated in previous studies.
Asked how the findings presented by Gandhi might affect the outlook on TB interventions, Wilkinson says: “Whilst close household exposure to infectious tuberculosis should prompt clinical evaluation especially if there are symptoms, finding a close contact by conventional contact tracing approaches is far from invariable. Therefore, in high incidence environments like South Africa more attention needs to be placed on mass radiographic (X-ray) and, or microbiological screening of asymptomatic persons.”
In a recent public lecture called ‘Hunting Bosons, Finding the Bummock’, Emeritus Professor in Medicine at the University of Cape Town, Robin Wood, former CEO of the Desmond Tutu Health Foundation, states: “I think we are changing the paradigm of tuberculosis.” He notes that research now targets “hidden reservoirs of TB transmission beyond visible, symptomatic cases… [as] TB silently spreads within communities through carriers who exhibit no symptoms yet contribute to transmission.” Asked about Gandhi’s findings, Wood told Spotlight he would reserve comment until the data is submitted for further peer review and publication.
Study details
The 305 respondents in the CONTEXT study were patients with extensively drug-resistant TB or pre-extensively drug-resistant TB. They were diagnosed between 2019 and 2022 in the eThekwini, Ilembe, Umgungundlovu, and Ugu regions. The average age was 36 years, with 137 (45%) women and 216 (73%) people living with HIV.
The study was conducted in collaboration with the Durban-based Centre for the AIDS Programme of Research in South Africa (CAPRISA).
“CAPRISA played a leadership role in conceptualising the science, development of the protocol and data collection instruments, oversight of all aspects of field work, including screening and enrolling patients, obtaining informed consent from patients or their proxy’s, field and laboratory data collection, data verification and data clean-up activities for all data used in this study,” says CAPRISA’s deputy director, Professor Kogieleum Naidoo.
CONTEXT was funded through the United States National Institutes of Health (NIH), the world’s largest health research funder which has in recent weeks terminated several grants in South Africa and elsewhere. “The funding period has ended,” says Gandhi. “Now we’re analysing all of the data, so it won’t be impacted by any changes happening at NIH.”
The rugby season is kicking off in schools across South Africa and players, parents, coaches and referees are preparing for exciting, yet physically demanding matches. In many sports, injuries are an unfortunate, common occurrence. Rugby, inherently a contact sport, also carries the inevitable risk of head injuries, ranging from minor concussions to severe Traumatic Brain Injuries (TBIs).
The importance of early detection
The early detection of head injuries is essential for effective treatment and preventing further complications. In many cases, the symptoms of a concussion or TBIs may not be immediately apparent and athletes may continue playing which can lead to further damage.
Accurate diagnosis and management of head injuries require a combination of clinical evaluation and advanced imaging techniques. Dr Hofmeyr Viljoen, radiologist at SCP Radiology talks about the nature of these injuries, the critical role radiology plays in diagnosing and managing them and what preventative measures can be taken.
Understanding head injuries in rugby
Dr Viljoen explains that there are several types of head injuries common in rugby. ‘The most frequent is concussion, a mild traumatic brain injury occurring when the brain is jolted inside the skull from an impact or violent movement. Concussions can be mild or lead to significant short and long-term issues. Occasionally, with more severe injuries we see skull fractures, contusions and haemorrhage surrounding the brain. These require urgent diagnosis and management.’
Recognising the symptoms
He emphasises awareness of concussion symptoms, including headaches, dizziness, nausea, confusion, memory problems, sensitivity to light and difficulty concentrating. ‘Immediate recognition is vital,’ he explains. ‘A player with any of these symptoms must be removed from play immediately to prevent further injury.’
The role of radiology
Radiology plays an essential part in accurately diagnosing the extent of head injuries. According to Dr Viljoen, Computed Tomography (CT) scans are always the first imaging method used in emergency settings. Although patients with concussion typically do not have significant imaging findings, it is crucial to image those patients with severe concussion or atypical symptoms. ‘CT scans rapidly detect serious issues like fractures, brain swelling and bleeding, providing crucial information for urgent treatment decisions,’ he explains.
Magnetic Resonance Imaging (MRI) is used in situations requiring more detailed evaluation, particularly when concussion symptoms persist or worsen. ‘MRI excels in identifying subtle injuries, such as microbleeds and brain swelling, often missed by CT scans,’ says Dr Viljoen. Unlike CT scans, MRI does not use radiation, making it a safer option for repeated assessments over time.
Advanced imaging methods
Emerging imaging techniques, such as Diffusion Tensor Imaging (DTI), show promise for better understanding and management of head injuries, especially the subtle effects of concussions. ‘DTI helps identify damage to the brain’s white matter, potentially guiding return-to-play decisions and treatment strategies,’ notes Dr Viljoen.
Understanding possible complications – Second Impact Syndrome (SIS)
SIS is a rare but extremely serious condition that occurs when a person sustains a second concussion before fully recovering from an initial concussion. This second injury doesn’t have to be severe to trigger SIS – it can even be minor – but it causes rapid and severe brain swelling (cerebral oedema).
The brain’s ability to regulate its blood flow and pressure is compromised following the initial concussion, making it vulnerable to catastrophic swelling after a subsequent impact. Symptoms can escalate quickly, often within minutes, including loss of consciousness, severe headache, dilated pupils, respiratory failure and even death. Young athletes are especially vulnerable to SIS. Due to its rapid progression and severity, SIS is considered a medical emergency requiring immediate intervention.
Preventing SIS involves strictly adhering to concussion management protocols, ensuring full recovery after any head injury and carefully monitoring symptoms before returning to sports or high-risk activities.
Addressing Chronic Traumatic Encephalopathy (CTE)
Dr Viljoen says CTE is a long-term degenerative brain condition linked to repeated head impacts. ‘CTE is challenging because currently, it can only be definitively diagnosed after death. However, ongoing research aims to develop methods to detect CTE in living patients, potentially using advanced imaging techniques like Positron Emission Tomography (PET).’ Most research is focused on advancing non-invasive methods to see what is happening inside the brain of a living person and to track it over time.
Common causes of head injuries in rugby
These primarily arise from the high-impact nature of the sport, with tackling identified as a significant risk factor. Tackling, particularly when performed incorrectly or at a dangerous height, frequently leads to head trauma. Young players are especially vulnerable as their tackling techniques may not yet be fully developed, increasing the likelihood of injury. Teaching safe and correct tackling methods early is a way to mitigate these risks
Rugby’s dynamic gameplay often results in players being brought down forcefully or falling awkwardly. Even with protective gear, the impact of the head striking the playing surface can lead to concussions or more severe trauma
Due to the speed and intensity of the game, unintended impacts between players are inevitable. These include clashes of heads or impacts from knees and elbows, which can result in injuries ranging from mild concussions to more severe brain injuries. Preventative strategies and safer playing practices can reduce these risks
Prevention remains critical
Dr Viljoen emphasises the importance of proper training: ‘Educating young players on safe tackling techniques and enforcing protective protocols significantly reduces injury risks. Protective gear like headguards can minimise superficial injuries, though it does not prevent concussions.’
He also stresses the importance of concussion protocols. ‘Coaches at schools and clubs must rigorously apply concussion management strategies, ensuring players are adequately assessed and cleared by medical professionals before returning to the field.’ Under-reporting in schoolboy ruby often occurs because the player either wants to stay in the game and/or doesn’t recognise the symptoms of concussion.
Dr Viljoen concludes, ‘Rugby is a fantastic sport for building teamwork and resilience but player safety must always come first. Through awareness, timely medical intervention and proper preventative strategies, we can significantly reduce the risk and severity of head injuries, allowing young athletes to safely enjoy the game they love.’
