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.’
Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0
Cervical artery dissection is a tear in an artery in the carotid or vertebral artery, and can result in blood clots that cause stroke. A new study has found almost a five-fold increase in the number of U.S. hospitalisations for cervical artery dissection over a 15-year period. The study is published on April 2, 2025, online in Neurology®, the medical journal of the American Academy of Neurology (AAN).
A dissection in the artery wall is most often caused by trauma due to motor vehicle accidents but can also occur with smaller injuries. Heavy lifting has also been shown to cause dissection in some people.
“Cervical artery dissection is an important cause of stroke, especially in people under 50, so it is crucial to detect it right away,” said Shadi Yaghi, MD, of Brown University in Providence, Rhode Island. “Strokes that are not fatal can lead to long-term disability, poor mental health and reduced quality of life. Our research found a dramatic increase in the number of hospitalisations for cervical artery dissection with rates rising steadily year over year.”
For the study, researchers reviewed 15 years of U.S. health data to identify 125 102 people hospitalised for cervical artery dissection. Participants had an average age of 51, and just over half had a stroke at the same time as dissection. Of all participants, 65% were white, 10% were Black, 8% were Hispanic, 3% were Asian or Pacific Islander, and 14% were of other racial groups. Researchers compared the number of hospitalisations to U.S. Census data to determine the annual rate of cervical artery dissections. They then calculated the average annual percentage change in those rates.
Researchers found the number of dissections increased from 11 cases per one million people in 2005 to 46 cases per one million people in 2019, with an average annual increase of 10%. Results were similar for both female and male participants. The average annual increase for Hispanic participants was 16%; for Black participants it was 13%, Asian participants, 12% and white participants, 8%.
Researchers also found a greater average annual increase among people 65 and older at 12% compared to 8% for people under 65.
“Possible reasons for this nearly five-fold increase over 15 years include greater awareness of cervical artery dissection by health care professionals, better access to imaging to help identify it and an overall increase in this condition for which a cause has yet to be determined,” said Yaghi. “Given the rising incidence of cervical artery dissection, our study underscores the importance of finding prevention strategies as well as new treatments to reduce the risk of stroke.” A limitation of the study was that the hospital admission data does not include undiagnosed or untreated cases, so the number of cases may be even higher.
An unusual public health policy in Wales may have produced the strongest evidence yet that a vaccine can reduce the risk of dementia. In a new study led by Stanford Medicine, researchers analysing the health records of Welsh older adults discovered that those who received the shingles vaccine were 20% less likely to develop dementia over the next seven years than those who did not receive the vaccine.
The remarkable findings, published April 2 in Nature, support an emerging theory that viruses that affect the nervous system can increase the risk of dementia. If further confirmed, the new findings suggest that a preventive intervention for dementia is already close at hand.
Lifelong infection
Shingles, a viral infection that produces a painful rash, is caused by the same virus that causes chicken pox — varicella-zoster. After people contract chicken pox, usually in childhood, the virus stays dormant in the nerve cells for life. In people who are older or have weakened immune systems, the dormant virus can reactivate and cause shingles.
Dementia affects more than 55 million people worldwide, with an estimated 10 million new cases every year. Decades of dementia research has largely focused on the accumulation of plaques and tangles in the brains of people with Alzheimer’s, the most common form of dementia. But with no breakthroughs in prevention or treatment, some researchers are exploring other avenues — including the role of certain viral infections.
Previous studies based on health records have linked the shingles vaccine with lower dementia rates, but they could not account for a major source of bias: People who are vaccinated also tend to be more health conscious in myriad, difficult-to-measure ways. Behaviors such as diet and exercise, for instance, are known to influence dementia rates, but are not included in health records.
“All these associational studies suffer from the basic problem that people who get vaccinated have different health behaviours than those who don’t,” said Pascal Geldsetzer, MD, PhD, assistant professor of medicine and senior author of the new study. “In general, they’re seen as not being solid enough evidence to make any recommendations on.”
Markus Eyting, PhD, and Min Xie, PhD, postdoctoral scholars in primary care and population health, are the study’s co-lead authors.
A natural experiment
But two years ago, Geldsetzer recognized a fortuitous “natural experiment” in the rollout of the shingles vaccine in Wales that seemed to sidestep the bias. The vaccine used at that time contained a live-attenuated, or weakened, form of the virus.
The vaccination program, which began Sept. 1, 2013, specified that anyone who was 79 on that date was eligible for the vaccine for one year. (People who were 78 would become eligible the next year for one year, and so on.) People who were 80 or older on Sept. 1, 2013, were out of luck — they would never become eligible for the vaccine.
These rules, designed to ration the limited supply of the vaccine, also meant that the slight difference in age between 79- and 80-year-olds made all the difference in who had access to the vaccine. By comparing people who turned 80 just before Sept. 1, 2013, with people who turned 80 just after, the researchers could isolate the effect of being eligible for the vaccine.
The circumstances, well-documented in the country’s health records, were about as close to a randomized controlled trial as you could get without conducting one, Geldsetzer said.
The researchers looked at the health records of more than 280 000 older adults who were 71 to 88 years old and did not have dementia at the start of the vaccination program. They focused their analysis on those closest to either side of the eligibility threshold — comparing people who turned 80 in the week before with those who turned 80 in the week after.
“We know that if you take a thousand people at random born in one week and a thousand people at random born a week later, there shouldn’t be anything different about them on average,” Geldsetzer said. “They are similar to each other apart from this tiny difference in age.”
The same proportion of both groups likely would have wanted to get the vaccine, but only half, those almost 80, were allowed to by the eligibility rules.
“What makes the study so powerful is that it’s essentially like a randomised trial with a control group — those a little bit too old to be eligible for the vaccine — and an intervention group — those just young enough to be eligible,” Geldsetzer said.
Protection against dementia
Over the next seven years, the researchers compared the health outcomes of people closest in age who were eligible and ineligible to receive the vaccine. By factoring in actual vaccination rates — about half of the population who were eligible received the vaccine, compared with almost none of the people who were ineligible — they could derive the effects of receiving the vaccine.
As expected, the vaccine reduced the occurrence over that seven-year period of shingles by about 37% for people who received the vaccine, similar to what had been found in clinical trials of the vaccine. (The live-attenuated vaccine’s effectiveness wanes over time.)
This huge protective signal was there, any which way you looked at the data.”
By 2020, one in eight older adults, who were by then 86 and 87, had been diagnosed with dementia. But those who received the shingles vaccine were 20% less likely to develop dementia than the unvaccinated.
“It was a really striking finding,” Geldsetzer said. “This huge protective signal was there, any which way you looked at the data.”
The scientists searched high and low for other variables that might have influenced dementia risk but found the two groups to be indistinguishable in all characteristics. There was no difference in the level of education between the people who were eligible and ineligible, for example. Those who were eligible were not more likely to get other vaccinations or preventive treatments, nor were they less likely to be diagnosed with other common health conditions, such as diabetes, heart disease and cancer.
The only difference was the drop in dementia diagnoses.
“Because of the unique way in which the vaccine was rolled out, bias in the analysis is much less likely than would usually be the case,” Geldsetzer said.
Nevertheless, his team analyzed the data in alternate ways — using different age ranges or looking only at deaths attributed to dementia, for example — but the link between vaccination and lower dementia rates remained.
“The signal in our data was so strong, so clear and so persistent,” he said.
Stronger response in women
In a further finding, the study showed that protection against dementia was much more pronounced in women than in men. This could be due to sex differences in immune response or in the way dementia develops, Geldsetzer said. Women on average have higher antibody responses to vaccination, for example, and shingles is more common in women than in men.
Whether the vaccine protects against dementia by revving up the immune system overall, by specifically reducing reactivations of the virus or by some other mechanism is still unknown.
Also unknown is whether a newer version of the vaccine, which contains only certain proteins from the virus and is more effective at preventing shingles, may have a similar or even greater impact on dementia.
Geldsetzer hopes the new findings will inspire more funding for this line of research.
“At least investing a subset of our resources into investigating these pathways could lead to breakthroughs in terms of treatment and prevention,” he said.
In the past two years, his team has replicated the Wales findings in health records from other countries, including England, Australia, New Zealand and Canada, that had similar rollouts of the vaccine. “We just keep seeing this strong protective signal for dementia in dataset after dataset,” he said.
But Geldsetzer has set his sights on a large, randomized controlled trial, which would provide the strongest proof of cause and effect. Participants would be randomly assigned to receive the live-attenuated vaccine or a placebo shot.
“It would be a very simple, pragmatic trial because we have a one-off intervention that we know is safe,” he said.
Geldsetzer is seeking philanthropic funding for the trial as the live-attenuated vaccine is no longer manufactured by pharmaceutical companies.
And such a trial might not take long to see results. He pointed to a graph of the Wales data tracking the dementia rates of those who were eligible and ineligible for the vaccine. The two curves began to separate in about a year and a half.
The idea that autism is caused by vaccines has recently been revived by Robert F. Kennedy Jr., the presumptive nominee for US Secretary of Health and Human Services, as well as by president-elect Donald Trump. When asked about vaccines at a recent press conference, Trump reportedly said there was “something wrong” with rising autism rates, adding: “We’re going to find out about it.”
From a research perspective, there is little left to discover about vaccines used in long-standing nationwide vaccine programmes, such as diphtheria, tetanus, whooping cough, polio, measles, mumps and rubella. There is strong data from different countries showing that these vaccines do not cause autism or underlie the vast increase in autism diagnosis rates. So why do suspicions that vaccines cause autism remain?
1. Unawareness of evidence
Reliably and accurately communicating research results to the public is difficult. Research results usually stay in small research or clinical communities. Research is rarely accessible and researchers have few incentives to communicate findings outside of their scientific channels.
Popular media is typically superficial and often primarily interested in controversy that generates public attention.
2. Challenges understanding the science
Science is complicated and in medicine there are rarely absolute truths. The public, however, might expect clear consensus or have difficulty grasping the precise nuance of the science and its findings.
Evidence shows that vaccines do not cause autism or are the reason for increasing diagnosis rates. But it is also in the nature of science that it can neither verify nor exclude totally that vaccines contribute to autism in single individuals.
They protect against viruses and bacteria that cause significant levels of death and human suffering. Vaccine programmes thus have a good risk-to-benefit ratio but are not perfect.
3. Doubts of science
The public may have doubts about science and scientists. Science often delivers probabilities and models, not absolute truths.
This might be disappointing or misunderstood as being no better than individual attitudes or opinions. Although not true for vaccines and autism, evidence can be contradictory and difficult to replicate, reinforcing public doubts.
This success has made most diseases invisible in many countries today. The absence of these diseases generates implicit beliefs that vaccinations are unnecessary.
5. Vaccines cause immune reaction
To reach the goal of immunisation, vaccines must cause an immune reaction. Therefore, a transient inconvenient physical reaction is a sign of success, and the logic of vaccination.
This alone might be counterintuitive and feed doubts about vaccinations. Compared to other drugs, only the side-effects are experienced, and the main effect is preventive, not immediately experienced.
6. Parallelism of events
Autism is a neurodevelopmental condition commonly appearing in the first years of life. Initial autistic behaviour may coincide by chance with vaccination time points or follow them and mix with immune reactions.
Making a connection between vaccination and the appearance of autism in these cases is inevitable. But correlation is not causation.
7. Drugs in infancy without an emergency
Ethical issues arise when people make decisions for others regarding drugs or feel coerced to take them. This is particularly true for infancy where parents must consent for their babies.
It can feel intuitively wrong to interfere with nature and invasive to give a series of shots to a fragile human being in early development in the absence of a medical emergency.
8. Actual harms from less-well established vaccines
Benefits and risks cannot be generalised across all vaccines. Vaccines that are part of long-standing vaccination programmes have good evidence to back them, indicating a convincing risk-benefit ratio.
New vaccines are not ensured in the same way. For instance, the swine flu vaccine during the 2009 pandemic is suspected of having caused 1300 cases of narcolepsy in Europe.
We must distinguish between well-established vaccines and those developed within a short period. It seems that necessary discussions around the safety of less well-established vaccines affect trust in established ones.
9. Polarised debate of vaccines
Open societies build on trust, freedom of speech and debate – but also on shared responsibility. Recent years have seen a polarisation of views around many topics, including vaccinations, not at least fuelled by the COVID crisis.
The urgency of the situation and need for solidarity left little space and time for discussion in society and marginalised or stigmatised even moderate sceptics. The latter has surely harmed trust in vaccines more generally.
Emerging evidence suggests that lycopene—a natural plant extract—may have antidepressant properties. New research in Food Science & Nutrition reveals the mechanisms behind its antidepressant effects.
Lycopene is a carotenoid, related to beta-carotene and gives some vegetables and fruits (eg, tomatoes, grapefruit) a red colour. Lycopene is a powerful antioxidant that might help protect cells from damage.
In mice with depressive-like behaviours, brain analyses revealed impairments in the hippocampus. Lycopene treatment lessened these impairments and reversed the animals’ depressive-like traits.
Lycopene treatment boosted the expression of brain-derived neurotrophic factor (BDNF), a protein with roles in many aspects of brain function. Experiments indicated that a signalling pathway involving BDNF (called the BDNF-TrkB pathway, which helps regulate learning, memory, and communication between neurons) is inhibited in mice with depression, and that lycopene treatment alleviates this inhibition.
The study “offers an effective avenue for the development of novel antidepressant therapies,” the authors wrote. “We plan to conduct further verification in future studies and include multiple brain regions in our research.”
