The rhythmic waves of electric pulses produced by neurons during sleep have long fascinated science and defied explanation. Slow brain waves are associated with restful, refreshing sleep. Now, scientists have found that brain waves help flush waste out of the brain during sleep. Individual nerve cells coordinate to produce rhythmic waves that propel fluid through dense brain tissue, washing the tissue in the process. This finding could help lead to new ways to treat diseases such as Alzheimer’s.
“These neurons are miniature pumps. Synchronised neural activity powers fluid flow and removal of debris from the brain,” explained first author Li-Feng Jiang-Xie, PhD, a postdoctoral research associate in the Department of Pathology & Immunology. “If we can build on this process, there is the possibility of delaying or even preventing neurological diseases, including Alzheimer’s and Parkinson’s disease, in which excess waste – such as metabolic waste and junk proteins – accumulate in the brain and lead to neurodegeneration.”
The Washington University School of Medicine in St. Louis researchers published their findings in Nature.
In carrying out the energy-demanding tasks of the brain’s functions, brain cells consume nutrients and create metabolic waste, which must be disposed of.
“It is critical that the brain disposes of metabolic waste that can build up and contribute to neurodegenerative diseases,” said Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator. Kipnis is the senior author on the paper. “We knew that sleep is a time when the brain initiates a cleaning process to flush out waste and toxins it accumulates during wakefulness. But we didn’t know how that happens. These findings might be able to point us toward strategies and potential therapies to speed up the removal of damaging waste and to remove it before it can lead to dire consequences.”
But the dense brain makes cleaning difficult. Cerebrospinal fluid surrounding the brain enters and weaves through intricate cellular webs, collecting toxic waste as it travels. Upon exiting the brain, contaminated fluid must pass through a barrier before spilling into the lymphatic vessels in the dura mater, which envelopes the brain. But what powers the movement of fluid into, through and out of the brain?
Studying the brains of sleeping mice, the researchers found that neurons drive cleaning efforts by firing electrical signals in a coordinated fashion to generate rhythmic waves in the brain, Jiang-Xie explained. They determined that such waves propel the fluid movement.
The research team silenced specific brain regions so that neurons in those regions didn’t create rhythmic waves. Without these waves, fresh cerebrospinal fluid could not flow through the silenced brain regions and trapped waste couldn’t leave the brain tissue.
“One of the reasons that we sleep is to cleanse the brain,” Kipnis said. “And if we can enhance this cleansing process, perhaps it’s possible to sleep less and remain healthy. Not everyone has the benefit of eight hours of sleep each night, and loss of sleep has an impact on health. Other studies have shown that mice that are genetically wired to sleep less have healthy brains. Could it be because they clean waste from their brains more efficiently? Could we help people living with insomnia by enhancing their brain’s cleaning abilities so they can get by on less sleep?”
Brain wave patterns change throughout sleep cycles. Of note, taller brain waves with larger amplitude move fluid with more force. The researchers are now interested in understanding why neurons fire waves with varying rhythmicity during sleep and which regions of the brain are most vulnerable to waste accumulation.
“We think the brain-cleaning process is similar to washing dishes,” neurobiologist Jiang-Xie explained. “You start, for example, with a large, slow, rhythmic wiping motion to clean soluble wastes splattered across the plate. Then you decrease the range of the motion and increase the speed of these movements to remove particularly sticky food waste on the plate. Despite the varying amplitude and rhythm of your hand movements, the overarching objective remains consistent: to remove different types of waste from dishes. Maybe the brain adjusts its cleaning method depending on the type and amount of waste.”
The gut has considerable plasticity among animals, shrinking as much 50% in cases of fasting such as hibernating and able to rapidly return to normal size on refeeding. Now, scientists from the University of Copenhagen used fruit flies to investigate the signalling mechanisms and cellular changes that regulate this rapidly renewable tissue, which could reveal insights into diseases such as colorectal cancer. Their results are published in Nature Communications.
“Taking advantage of the broad genetic toolbox available in the fruit fly, we have investigated the mechanisms underpinning nutrient-dependent gut resizing,” says Dr Ditte S. Andersen.
The results show that nutrient deprivation results in an accumulation of progenitor cells that fail to differentiate into the mature cells causing the gut to shrink.
Upon refeeding these stalled progenitor cells readily differentiate into mature cells to promote regrowth of the gut.
Ditte S. Andersen continues: “We have identified activins as critical regulators of this process. In nutrient restrictive conditions, activin signalling is strongly repressed, while it is reactivated and required for progenitor maturation and gut resizing in response to refeeding. Activin-dependent resizing of the gut is physiologically important as inhibition of activin signalling reduces survival of flies to intermittent fasting.”
Regulators of organ plasticity are essential for host adaptation to an ever-changing environment, however, the same signals are often deregulated in cancers. Indeed, mutations affecting activin signalling are frequent in cancer cells in a variety of tissues. This study provides a starting point for investigating the link between aberrant activin signalling and the development of colorectal cancers and sets the stage for exploring the efficiency of anti-activin therapeutic strategies in treating colorectal cancers.
As global temperatures continue to rise, a new study of 1.2 million births in Sydney over two decades has shown a strong association between the risk of pre-term birth and exposure to extreme hot temperatures in the third trimester of pregnancy. The data suggested that this association with extreme temperature might be reduced by greenery.
The findings suggest health services should consider preparing for an increase in preterm births as our climate warms.
The Monash University-led study, published in JAMA Pediatrics, looked at the relationship between preterm birth, exposure to high temperatures as well as the mitigating factor of exposure to trees and overall greenness. Excess heat was defined as trimester temperatures higher than the 95th percentile of trimester distributions over the 20-year period.
The study, led by A/Prof Shanshan (Shandy) Li from the Monash School of Public Health and Preventive Medicine, looked at 1.2 million births – including 63 144 preterm births – occurring in Sydney, between 2000 and 2020, using the New South Wales Midwives Data Collection.
The research team cross-referenced this data with historical temperature data, as well as tree cover and overall greenness levels derived from satellite images.
The research concluded that exposure to both daytime and night-time extreme heat in the third trimester was strongly associated with increased preterm birth risks, unlike the same exposure in either the first or second trimesters.
This association existed for all levels of area-level greenness, although the strength of the association was slightly diminished for women living in areas with more trees and other greenery, raising the intriguing possibility that greenness might ameliorate some of the excess risk from extreme heat exposure in the third trimester that deserves further study.
First author A/Prof Li is an expert in environmental impacts on children’s health.
She says, “The presence of greenery, especially trees, has the potential to mitigate heat levels and lower the risks of preterm birth associated with heat. Greenery also has positive physical and mental health impacts beyond just pregnancy and birth outcomes. We should be integrating heat mitigation strategies such as increasing green spaces into urban planning, to improve public health.”
According to Professor Yuming Guo, senior author on the study, and also from Monash University, there has been increasing but still limited epidemiological evidence linking prenatal environmental temperatures with birth outcomes.
“Emerging evidence suggests that night-time air temperature, particularly extreme night-time heat, significantly impacts health, including sleep and rest. Sleep quality and duration affects various aspects of health, and disturbances in these factors may have consequences for pregnancy outcomes,” he said.
“High night-time temperatures can disrupt circadian rhythms and potentially influence blood pressure, which may be an issue for pregnant individuals. Given the projected increase in extreme temperatures as our planet warms, understanding its impacts on birth outcomes and developing strategies to mitigate the risks becomes crucial.”
While it’s not surprising to spot teens wearing headphones and earbuds, it’s also becoming a widespread trend among younger children, a national poll suggests. Two in three parents say their child ages five to 12 uses personal audio devices, with half of parents of children ages five to eight reporting elementary-aged kids use a device.
Among parents whose children use headphones and earbuds, half say kids spend at least an hour a day using them. One in six say their child typically uses them for at least two hours, according to University of Michigan’s C.S. Mott Children’s Hospital National Poll on Children’s Health.
“Over recent years we’ve mostly been concerned about teens overusing audio devices. But earbuds have become increasingly popular and prevalent among younger kids, exposing them to more intense noise on a regular basis,” said Susan Woolford, MD, MPH, Mott paediatrician and co-director of the poll.
“Noise exposure risks to young children have historically involved loud singular events like concerts or fireworks, but parents may underestimate the potential harm from excessive use of listening devices. It may be difficult to know whether their child’s exposure to noise is healthy.”
Children are most likely to use these devices at home, school and in the car, report findings show. About a fourth of parents also say children occasionally use audio devices on airplanes while less than 10% say kids use them on the bus, outside or in bed.
Half of parents agree that headphones or earbuds help keep their child entertained.
The American Academy of Pediatrics released a statement in 2023 on the need to reduce noise risks to children, with increasing evidence that children and teens may be more exposed through personal listening devices.
Prolonged or extreme exposure to high volumes of noise can result in long term health issues, including hearing loss or tinnitus, Woolford says.
“Young children are more vulnerable to potential harm from noise exposure because their auditory systems are still developing. Their ear canals are also smaller than adults, intensifying perceived sound levels,” Woolford said.
Noise exposure among children can also affect their sleep, academic learning, language, stress levels and even blood pressure, she adds.
More parents of children aged 9–12 years than 5–8 years report their child uses headphones or earbuds and daily use was also more likely to be higher among the older age group, the poll suggests.
But only half of parents share they’ve tried to limit their child’s audio device usage, citing strategies such as asking the child to take a break, having set hours for use and using a timer.
Parents whose child uses headphones for more than two hours a day are also less likely to set time or volume limits, compared to parents who report less headphone use for their child.
Woolford offers four tips to reduce risks of noise exposure to children through headphones and earbuds:
Monitor volume levels
Parents can minimise the negative impact of audio device usage by monitoring and adjusting the child’s volume and time on devices, Woolford says. She recommends parents follow the 60/60 rule – children should be limited to no more than 60 minutes of audio devices a day at no more than 60% of the maximum volume.
The sound level on listening devices that are less than 70 dBA (relative loudness of decibels heard) are very unlikely to cause noise-related damage.
“A good way to tell if an audio device is too loud is if a child wearing headphones can’t hear you when you’re an arm’s length away,” she said.
Parents can also limit their child’s risk by setting specific hours for audio device use or using a timer to keep track.
Use noise cancelling or volume limiting headphones
Parents should consider the risk of noise exposure when purchasing audio devices for their child by checking the information on device packages to identify products that limit the volume.
But some products marketed as “kid safe,” Woolford warns, do not limit the volume to 70 decibels.
However, children should avoid using noise-cancelling listening devices in situations when perception of sounds is crucial for safety.
“Noise-cancelling devices may help prevent children from increasing the volume to levels that are too high,” Woolford said. “But these devices shouldn’t be used when a child is engaged in activities where it’s important to hear their surroundings for their safety, such as walking or bike riding.”
Ensure kids take breaks from personal listening devices
Parents should help children intentionally have daily ‘device-free’ time, Woolford says. This may involve putting away or locking the child’s audio devices when time limits are up.
They may also encourage kids to enjoy things like music on a low volume in their rooms instead of using earbuds to reduce noise intensity.
Personal audio devices should also be avoided when children are sleeping or at bedtime, Woolford says.
Be mindful of early signs of hearing loss
If parents feel their child may be at risk of hearing loss due to using audio devices, Woolford recommends checking with a paediatrician, an audiologist, or an ENT specialist.
“Early signs of hearing loss may include asking for repetition, hearing ringing noises often, speaking loudly to people nearby, delayed speech, or lack of reaction to loud noises,” Woolford says.
“Healthcare providers may be of assistance to parents by offering a simple explanation about hearing loss to help the child understand the reasons for limiting their use of audio devices.”
Taking antiretrovirals to prevent HIV infection is available in the form of pills, vaginal rings, and injections. (File photo: Nasief Manie/Spotlight)
A new HIV prevention injection is now available to a select number of people in South Africa. That a single shot provides two months of protection is one of the injection’s major selling points. In this story, Elri Voigt unpacks how much of the jab is available, who is choosing to get it and what other anti-HIV drugs are being rolled out.
By Elri Voigt for Spotlight
Earlier this month, a young person in Cape Town became one of the first people in the country to receive a new HIV prevention injection outside of a clinical trial. The injection contains a long-acting formulation of the antiretroviral drug cabotegravir (CAB-LA for short). It provides two months of protection against HIV infection per shot.
“We were excited and nervous at the same time because (we) didn’t know how this person is going to react to an injection,” said Pakama Mapukata, a nurse and study coordinator. She added that the first person who received the CAB-LA injection responded well and told her that the injection was less painful than an sexually transmitted infection (STI) injection they had to receive in the past.
While the injection is not readily available for most members of the public just yet, a select number of people in the country will be able to access it via several implementation studies, also called pilot projects. One of these pilots is a study called FAST PrEP, conducted by the Desmond Tutu Health Foundation (DTHF) in Cape Town. Technically, access to the injection is limited to a FAST PrEP sub study called Prepare to Choose.
Taking antiretrovirals to prevent HIV infection is referred to as pre-exposure prophylaxis (PrEP). PrEP is available in the form of pills, vaginal rings, and injections.
According to Elzette Rousseau, a social behavioural scientist and the lead co-investigator in the implementation team for FAST PrEP, on the first day it was offered, five people opted to get the CAB-LA shot. “The first two, at least, that came through was a young MSM [men who have sex with men] and one was a young woman, which is definitely exciting because that is the population that we would want to come to our services which will benefit most from it,” she said. As of 21 February, 19 injections in total had been administered.
‘Real-world experience’
Professor Linda-Gail Bekker, Chief Executive Officer of the DTHF and Principal Investigator of the study, explained that once CAB-LA demonstrated efficacy in phase three clinical trials, it was decided to first do some implementation science studies in the country, alongside the other new PrEP option which is the dapivirine vaginal ring (DPV-VR), before rolling it out in the public sector.
Both the CAB-LA injection and the dapivirine ring have been approved by the South African Health Products Regulatory Authority (SAHPRA). Prevention pills, also called oral PrEP, were approved several years earlier and are already widely available in the public sector and at pharmacies.
She explained the idea is that these implementation studies can help transition the product from the clinical trial setting to a real-world rollout in the public sector. Essentially the pilots would serve as a way of introducing the injectable and the ring on a smaller scale and lessons learnt from the pilots could be used to inform the future, larger rollout of these products. It also helps pick up any potential issues or safety concerns that may not have been seen in the clinical trials.
She added that pilot projects also help inform what the demand for a product like CAB-LA and the DPV-VR will be, which can help with advocacy efforts and give the manufacturers and companies who create generic products an idea of whether it’s worth investing in these products.
“There really are limited pilots going on in the country to date,” Bekker said. The pilots that are offering CAB-LA in addition to the DTHF are being conducted by Ezintsha and Africa Health Research Institute (AHRI), as well as the Wits Reproductive Health and HIV Institute (Wits RHI). Spotlight reported on this in-depth last year.
CAB-LA delays
Bekker told Spotlight the volumes of CAB-LA available in the country remain constrained for now.
While SAHPRA approved the injection in late 2022, limited supply and the product’s high price has limited uptake around the world. A recent HIV investment case for South Africa found the injection not to be cost-effective at the current price compared to PrEP in the form of pills. For now, the only supplier of CAB-LA is the pharmaceutical company ViiV Healthcare. Generic products are anticipated to enter the market in three to four years.
Despite SAHPRA approval for the product, the pilot projects have experienced delays in getting CAB-LA to their participants. As Spotlight reported last year, the National Department of Health stated that there were challenges getting the CAB-LA injections donated for the implementation studies into the country as the packaging did not meet South African regulatory requirements.
Bekker said that an alternative is to import CAB-LA through a phase 3b study (in this case the Prepare to Choose study), approved by SAHPRA’s Clinical Trial committee. Writing up protocols and having the study approved by an ethics committee and SAHPRA took some time, and once it was approved, CAB-LA still needed to be imported and ViiV Healthcare had to ramp up manufacturing to meet demand.
Bekker told Spotlight that to date, CAB-LA has not yet been purchased by the National Department of Health for distribution to the public, and the only other way to get CAB-LA into the country will be through a donation by the United States President’s Emergency Plan for AIDS Relief (PEPFAR).
“PEPFAR has been able to import the product into Zambia and Malawi…as the first two PEPFAR countries to get it as a PEPFAR donated public rollout and we hope South Africa is in that queue further down the line,” she said.
The Prepare to Choose Study
At the moment, Prepare to Choose can only offer CAB-LA to a few hundred people. Bekker said that ideally, they would have wanted to offer all their FAST PrEP clients a three-way choice of either the vaginal ring, oral PrEP pills or CAB-LA. But for now, CAB-LA is only being offered within Prepare to Choose, which is a single-nested sub study within FAST PrEP.
Mapukata, who was present during the first CAB-LA injection in the implementation study, said it will be interesting to see what participants choose now that they have an additional PrEP option. “People have been waiting for injection for the longest time, so we are seeing lots of excitement from the participant side,” she said.
Rousseau told Spotlight that Prepare to Choose currently has enough CAB-LA doses for 900 participants over an 18-month period.
She said they have thus far observed that “people are still choosing what [PrEP option] suits them” when offering existing or potential FAST PrEP participants the choice to access CAB-LA.
So far those who have chosen CAB-LA are primarily adolescent girls and young women with an average age of 22. Some have been on PrEP before, while others are starting PrEP for the first time. “In that cohort we know that the burden of HIV exists, so that’s encouraging at this point,” Rousseau said.
Trends observed in FAST PrEP
FAST PrEP is being implemented at 12 public sector health facilities in the Klipfontein and Mitchells Plain Health Sub-Districts in the Western Cape, as well as in four mobile clinics that operate in the area. Since the start of FAST PrEP, just under 11 000 participants have enrolled, according to Rousseau. This means that around 11 000 people have accessed either prevention pills or the DPV-VR through the study.
When FAST PrEP started, the assumption was that the study can enrol between 20 000 and 23 000 participants, but it is not necessarily targeting to enrol that exact number of participants. Rousseau added that the study currently has funding to continue offering PrEP until late next year but access to these options may potentially continue beyond that.
The study reaches participants in public sector healthcare facilities by having two peer navigators in each facility. These peer navigators are young people trained and employed by the study coordinators. They can educate and counsel young people about FAST PrEP. The study coordinators also offer training, particularly sensitisation training, to nurses and other staff members.
The four mobile clinics travel around the Klipfontein and Mitchells Plain Health Sub-Districts, particularly where there is a high incidence of HIV, as well as spaces where young people are present. These include 16 secondary schools in the area where the mobile clinics have permission to enter the school grounds.
Demand for the DPV-VR
Rousseau told Spotlight that so far, just under 200 women in the study have chosen to use the DPV-VR. However, it’s important to note that within the whole study population, not everyone is eligible to use the ring. It is currently being offered to women who are over 18, not pregnant and not breastfeeding.
She added that for participants who are eligible for both the ring and oral PrEP, the pill is still more popular – with a rough estimate of around 15% of eligible participants opting for the ring. Most participants, at this stage, who choose to use the ring are those who have tried oral PrEP first and struggle to take pills daily or found it doesn’t suit their lifestyle. Very few participants to date have started on the ring and then switched to the daily pill.
Dapivirine vaginal ring. Credit: Columbia University Mailman School of Public Health
She said the demographics of who prefers the ring over oral PrEP haven’t been explored in-depth, but it’s something that the study will be looking at and analysing data on in future.
Bekker added to this saying: “We always expected it to be a bit of a niche product because you know definitely for many the idea of swallowing a pill is perhaps an easier concept than using a vaginal ring. So, it has started slowly, we’ve now administered hundreds as opposed to thousands of rings.”
She noted that interest in the ring has built overtime and is starting to pick up more. “Our first, preliminary data suggests that the women who choose rings are coming back [for it] …they’ve decided they want to go that road and they’ve committed,” Bekker said.
Counselling for Choice
While the ring was found to be effective in two phase 3 trials, its efficacy in those trials was far from 100% and the evidence for the ring’s efficacy is generally less impressive than that for pills and the injection. Interpreting findings from PrEP trials is also somewhat muddied by whether or not pills are taken as prescribed, and the ring is used and replaced as prescribed – that a single shot provides two months of protection is one of the injection’s major selling points.
Compared to placebo, there was a 30% reduction in HIV infection for ring users in phase three trials, while there was a 50 to 60% reduction in infection when the ring went to open-label, Bekker noted.
She said that it has previously been observed that clinical trial efficacy results can differ from real-world results, particularly when it comes to HIV prevention. For instance, she said, oral PrEP in clinical trials initially showed no evidence of efficacy in the prevention of HIV in women. Yet, real-world evidence showed it works in all populations if taken as prescribed.
What both these cases have shown, according to Bekker, is that it’s not necessarily that the product isn’t working, it’s that the product isn’t always being used as intended. When it comes to the ring, she said, the drug within the ring is efficacious and will kill the virus, but the ring must be present at the time that the individual is exposed to HIV. “Once you take the ring out, the [prevention] effect is lost,” she said.
When asked how women are counselled about the ring in the FAST PrEP study, Bekker said it is done very carefully and with guidance of their peers – this is where the peer navigators play a big role.
FAST PrEP was designed using a lot of engagement from young people, Bekker said. For a year before the pilot started, a group of 100 young people from diverse populations were enrolled from the community to give feedback on how to design the pilot so it can best reach young people. This group also essentially helped troubleshoot the information coming from the pilot to ensure that the PrEP choices were communicated in an appropriate way.
“They are very instrumental at the moment in making sure that that message [on DPV-VR] is clearly communicated,” she said.
Bekker added that if an individual needs time to think about which PrEP option to use, they are advised to start with oral PrEP and that they can switch later if they want.
Mapukata explained how the counselling process plays out on the ground. Participants in FAST PrEP, once they have spoken to a peer navigator, are taken into a counselling room and given a quiz where their scores are used to indicate what PrEP option might work for them. This is used as a starting point to counsel participants about the different PrEP options and which options they are eligible for and most comfortable using.
“It’s a lot of counselling that goes in before that choice [of PrEP] is made,” Mapukata said.
Young people who are members of the FAST PrEP youth reference group speak of the project in glowing terms. “And it’s so nice because you have a variety to choose from, you’re not obligated [to only] be on PrEP, on the oral, because there’s a variety of options,” one of them told Spotlight.
In the northern hemisphere, children born in October are most likely to be vaccinated for the flu in October – and are least likely to be diagnosed with influenza, according to results of the first large-scale study of optimal timing for the flu shot.
The study, by researchers from the Department of Health Care Policy in the Blavatnik Institute at Harvard Medical School, amplifies public health guidance that encourages getting flu vaccinations in October for those in the northern hemisphere. The findings appear in the BMJ.
“There are a lot of variables when it comes to the timing and severity of flu season or a person’s risk of getting sick, and many of those are out of our control,” said Anupam Jena, the Joseph P. Newhouse Professor of Health Care Policy at HMS, physician at Massachusetts General Hospital, and senior author of the study. Christopher Worsham, HMS assistant professor of medicine and critical care physician at Mass General, led the study.
“One thing we have some control over is the timing of the shot,” Jena said, “and it looks like October is indeed the best month for kids to get vaccinated against the flu.”
In January the U.S. Centers for Disease Control and Prevention reported at least 150,000 hospitalizations and 9,400 deaths due to flu as of the time of the report and noted that high demand for hospital care for influenza has contributed to strained hospital capacity in some parts of the country. Over the past decade in the U.S., between one and 199 children have died of influenza each flu season. Across the years, most children who die are not fully vaccinated against the flu.
Part of the reason the timing of the shot is tricky is the way the immune system responds to a vaccine. If a person gets the shot too early, their immunity may fade by the time flu season peaks. If they wait too long, their body may not have time to build immunity strong enough to protect against the peak level of infections.
How soon is too soon, and how late is too late?
While public health recommendations in the U.S. have long promoted September and October flu shots, there has never been a randomised clinical trial to test the best timing, nor a large-scale effort to see how likely people who get vaccinated in other months are to get sick, Jena said.
When Jena was at a late summer meeting in 2022, he mentioned that his arm was sore from getting his flu shot. A colleague asked whether he was concerned about his immunity waning before flu season.
“It hadn’t occurred to me to check if one month or the other might make a big difference,” Jena said. “When we looked at the science, we were surprised that no one had ever looked at the question in a big population.”
Organising a clinical trial would require a lot of time and resources to coordinate the random distribution of flu jabs across hundreds or thousands of people.
But Jena, Worsham, and study co-author Charles Bray, HMS research assistant in health care policy, had a good idea where they could find an already randomized study population.
The surprising link between birth dates and childhood flu vaccination
In prior research reported in the New England Journal of Medicine in 2020, Jena and Worsham documented the way birth month determines how likely it is that children get the flu shot at all.
Young children in the U.S. tend to get their yearly checkup around their birthday, and it’s also when they get most of their vaccines. Children with spring and summer birthdays often don’t get the flu shot because it’s not available when they go for their annual visit, and many parents don’t make an extra trip for it.
The NEJM research was meant to highlight the importance of promoting the flu vaccine in the fall for children with birthday months that make it less likely that they will get the vaccine. Jena and Worsham realized they could also leverage this quirk of health care to study a ready-made distribution of children who get checkups – and flu shots – across all the months when the vaccine is commonly available.
Randomised by birthday
Studying children who got a flu shot in their birth month minimised certain factors related to the risk of infection that would have made it harder to measure the true impact of the timing of the shot.
For instance, families who proactively sought out shots in a non-birthday month might have done so because the child had a higher risk of catching the flu or because family members were more cautious and more likely to take actions that would protect them from the flu, such as handwashing and disinfecting.
For the BMJ study, Jena, Worsham, and Bray analysed the anonymised commercial health insurance records of more than 800 000 children in the U.S. from 2 to 5 years old who received influenza vaccines from 2011 to 2018.
The analysis showed that children born in October had the lowest rate of influenza diagnosis. For example, 2.7% of children born and vaccinated in October were diagnosed with the flu that season, compared to 3% of those born and vaccinated in August or January, 2.9% of those born and vaccinated in September or December, and 2.8% of those born and vaccinated in November.
The findings suggest that U.S. public health interventions focused on vaccination of young children in October may yield the best protection in typical flu seasons, the authors said.
“This study can help people pinpoint the best time to get flu vaccines for their children – especially the ones who weren’t born in October,” Worsham said.
“We’ve had several rough winters in a row for respiratory viruses, between COVID-19, RSV, and the flu,” Worsham said. “We need all the help we can get to keep people safe from these diseases.”
Finance Minister Enoch Godongwana tables his 2024 Budget during a joint seating of the National Assembly in the Cape Town City Hall. (Photo: National Treasury)
By Wanga Zembe, Donela Besada, Funeka Bango, Tanya Doherty, Catherine Egbe, Charles Parry, Darshini Govindasamy, Renee Street, Caradee Wright and Tamara Kredo
The 2024 national budget offers some glimmers but allocations for direct health benefits fall short of making a difference to people’s health and wellbeing. These include a ring-fenced allocation to crack down on corruption in health to inspire trust for theNational Health Insurance, taxing accessories for e-cigarettes, a jacked up child-support grant, clarity on plans dealing with climate change and its impacts on human health, and finally greater investment to enhance women’s capabilities alongside the Covid-19 grant, researchers from the South African Medical Research Council write exclusively for Spotlight.
The 2024 national budget presented last week by Finance Minister Enoch Godongwana contained several key elements that have an impact on systems, services and wellbeing from a health perspective.
Importantly, not only direct health spend, but budget allocated to social protection and climate infrastructure has implications for health outcomes such as nutrition, growth and food security. Health taxes, to address illness caused by alcohol, cigarettes and e-cigarettes amongst others, are also key revenue streams with taxation intended to deter use.
As researchers at the South African Medical Research Council we are dedicated to improving the health of people in South Africa through research and innovation. We wish to share some insights into positive areas in the budget and to point out areas where there are gaps with potentially dire consequences for the health of our nation.
In real terms, the health budget is shrinking.
Health has been allocated a total of R848-billion over the medium-term expenditure framework. This includes R11.6-billion to address the 2023 wage agreement, R27.3-billion for infrastructure and R1.4-billion for the National Health Insurance (NHI) grant. Compared to the medium-term budget policy statement in October last year, government is now adding R57.6-billion to pay salaries of teachers, nurses and doctors, among other critical services.
In real terms, the health budget is shrinking. The allocation to cover last year’s higher-than-anticipated wage settlement is a positive step to try to fill posts for essential health workers. But this allocation falls short of fully funding the centrally agreed wage deal, meaning that provincial health departments will be unable to fill all essential posts.
Treasury’s Chief Director for Health and Social Development, Mark Blecher, was quoted as saying that the “extra money would not be sufficient to hire all the recently qualified doctors who have been unable to secure jobs with the state, and provincial Health Departments will need to determine which posts should be prioritised”. He added: “There will be less downsizing, and more posts will be filled, but it is unlikely they all will be.”
South Africa has a ratio of only 7.9 physicians per 100 000 people in the public health system, while it has been estimated that there are more than 800 unemployed newly qualified doctors. Considering the health-workforce shortfalls, the amount of money allocated appears optimistic for service coverage for the increasing population.
The World Health Organization (WHO) considers building a health workforce a highly cost-effective strategy. Salaries continue to consume the largest share of provincial health budgets, estimated at 64% since 2018. The Human Resources for Health strategy lacks clarity on the implementation of workforce-planning approaches with significant implications for how provinces prioritise workforce cadres to keep up with the increasing needs – particularly in light of NHI.
Nutrition support on the decline
The Minister described protecting the budgets of critical programmes such as school-nutrition programmes, which includes almost 20 000 schools. He noted that the early childhood development (ECD) grant will be allocated R1.6-billion rising to R2-billion over the medium term.
Ensuring nutrition support to children under-five for optimal physical and cognitive growth is vital. The 2023 National Food and Nutrition Security Survey by the Human Sciences Research Council found that 29% of children under five in South Africa are stunted (short for their age). The proportion of children experiencing both acute and chronic under-nutrition has increased over the past decade. Stunted children are more likely to earn less and have a higher risk of obesity and non-communicable diseases such as diabetes and heart disease as adults.
Currently, only registered or conditionally registered Early Learning Programmes (ELPs) serving poor children (determined by income-means testing) are eligible to receive the ECD subsidy. This is not aligned with inflation and the real value of the R17 per child per day subsidy and the contribution to nutrition costs have decreased over time. The subsidy is not enough to cover the costs of running quality programmes, let alone the costs of providing nutritious meals. The World Bank suggests a minimum of R31 per child per day.
There is also concern about the children missed who attend informal or unregistered programmes. According to the 2021 Early Childhood Development Census, only 41% of ELPs are registered and only 33%, registered or not, receive the subsidy. Unregistered ELPs are more likely to be based in vulnerable communities and attended by children from vulnerable households. Further, although about 1.7 million children are enrolled in ELPs, enrolment rates vary across provinces from 40% in Gauteng to 26% in the Eastern Cape. This means many young children are not enrolled, and, of those enrolled, most do not benefit from the subsidy.
Child grants increase not keeping up with inflation
Child grants appear in the budget every year, but the increases do not keep up with inflation, and particularly not with the basket of goods needed for a growing child. In real terms grant amounts are decreasing – visible in the way hunger is increasing throughout the country, particularly in the Eastern Cape where uptake of social grants is very high.
The Social Relief of Distress Grant and women’s economic empowerment
As part of pandemic recovery efforts, we commend government for the roll-out of the Social Relief of Distress (SRD) grant and its plans to extend this beyond March 2025. While SRD continues to suffer implementation challenges related to the amount and roll-out; it presents an opportunity for renewed attention to a comprehensive and inclusive approach to women’s economic empowerment.
The recent Stats SA labour survey reported a higher unemployment rate among women (35.7%) versus men (30.7%). Our research also finds that women caregivers of children and adolescents living with HIV are particularly vulnerable to poor health and economic outcomes. Greater investment in programmes that enhance women’s opportunities alongside the SRD could promote the sustainability of pandemic-recovery efforts.
The NHI, health-system reforms and dealing with corruption in health
The Minister indicated that the allocation for NHI – government’s policy for implementing universal health coverage – demonstrates commitment to this policy. He also noted that there are a range of system-strengthening activities, that are key enablers of an improved public healthcare system, including strengthening the health-information system; upgrading facilities; enhancing management at district and facility level; and developing reference pricing and provider payment mechanisms for hospitals. He recognised that these require further development before NHI can be rolled out at scale.
The NHI allocation must show a tangible commitment to health-system reforms. Funding needs to be allocated for the creation of organisational infrastructure that ensures transparent, trustworthy decisions will be made about the benefits package and programmes to be funded. Specifically, funding for conducting Health Technology Assessments with credible processes that manage interests and ensure coverage decisions are informed by independent appraisal of the best-available evidence, measures of affordability, and with public input. Some areas of government already undertake such work, for example the National Essential Medicine Committee, but how these processes will expand beyond medicine to include decisions about health-systems arrangements and public-health interventions remain unclear, and apparently unfunded.
Undoubtedly, facilities need to be upgraded. It’s positive to see this as a named activity. It is however unclear how the upgrade of health facilities and quality of care will be ensured, given that tertiary infrastructure grants have been reduced due to underspending of conditional grants. Currently, health facilities’ quality is assessed by the Office of Health Standards Compliance whose role is to inspect and certify facilities. This is a prerequisite for accreditation under NHI. This means the watchdog agency will need adequate budget. Implementation research is also required to test out the different NHI public-private contracting models. Furthermore, a ring-fenced allocation to deal with corruption in health, would be welcomed and inspire trust for NHI.
‘Sin’ taxes vs ’health taxes’
The Minister proposed excise duties and above-inflation increases of between 6.7 and 7.2% for 2024/25 for alcohol products and indicated that tobacco-excise duties will be increased by 4.7% for cigarettes and cigarette tobacco and by 8.2% for pipe tobacco and cigars. And, based on inputs from citizens, the Minister also tabled an increase in excise duties on electronic nicotine and non-nicotine delivery systems (vapes).
While there may be a concern that increasing taxes on products consumed by the poor is regressive, there are ways to direct revenue gained back to those sub-populations and it’s not fair to deny them the benefits of consuming less alcohol products.
It is notable that excise taxes on wine have been increased to a greater percentage than spirits, but the health effects of alcohol come from the ethanol not the type of liquor product so it would make more sense to make the excise tax rate per litre of absolute alcohol equal across all products. The budget has not moved this forward in any meaningful way.
The proposed tax on tobacco products is not in line with WHO recommendations and is below inflation. This should be at least 70% of the retail price to have a positive impact on public health by reducing tobacco use, especially in a country with one of the highest tobacco-use rates in the region. In South Africa, the tax is currently between 50 – 60%. Although the tax on electronic cigarettes has increased, it is still below inflation. We hope that this increase will deter more young people from starting to use e-cigarettes and encourage current users to quit. We also hope that this increase is not just once-off and that future increases are made with the goal of reducing e-cigarette use.
Overall, the taxes on tobacco products and electronic nicotine and non-nicotine delivery systems are below inflation. This means that manufacturers can absorb the increases, and consumers may not be deterred from using them. This is a missed opportunity, as there is a clear link between these products and the development of non-communicable diseases, like hypertension, and the worsening of communicable diseases, like tuberculosis.
The impact of climate change on lives and livelihoods
Climate and health are closely related, with more attention being paid by the global research community to potential impacts of climate change and natural disasters on lives and livelihoods. The Minister noted a multi-layered risk-based approach to manage some of the fiscal risks associated with climate change. These include a Climate Change Response Fund; disaster-response grants; support and funding from multilateral development banks and international funders to support climate adaptation, mitigation, energy transition and sustainability initiatives; and, municipal-level adaptation and mitigation initiatives.
There are numerous health co-benefits to these strategies. For example, investing in renewable energy sources can improve air quality, leading to reduced respiratory illness. There is a need to highlight these co-benefits and to foster intersectoral collaboration.
Overall, from the perspective of health researchers, we note the mention of NHI plans, social protection, nutrition, health workforce, health taxes and climate. However, we all agree that the allocations for direct health benefits and to address social determinants of health, such as education and poverty-alleviation, fall short of what is recommended, from global and national research evidence, to make a difference to people’s health and wellbeing.
People living in ancient Eastern Arabia appear to have developed resistance to malaria following the appearance of agriculture in the region around five thousand years ago, a new study published its in Cell Genomics reveals.
DNA analysis of the remains of four individuals from Tylos-period Bahrain (300 BCE to 600 CE) – the first ancient genomes from Eastern Arabia – revealed the malaria-protective G6PD Mediterranean mutation in three samples.
The discovery of the G6PD Mediterranean mutation in ancient Bahrainis suggests that many people in the region’s ancient populations may have enjoyed protection from malaria.
In the present day, among the populations examined, the G6PD mutation is detected at its peak frequency in the Emirates, the study indicates.
Researchers discovered that the ancestry of Tylos-period inhabitants of Bahrain comprises sources related to ancient groups from Anatolia, the Levant and Caucasus/Iran.
The four Bahrain individuals were genetically more like present-day populations from the Levant and Iraq than to Arabians.
Experts from Liverpool John Moores University, the University of Birmingham Dubai, and the University of Cambridge worked with the Bahrain Authority for Culture and Antiquities and other Arabian institutes such as the Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, as well as research centres in Europe.
Lead researcher Rui Martiniano, from Liverpool John Moores University, commented: “According to our estimates, the G6PD Mediterranean mutation rose in frequency around five-to-six thousand years ago — coinciding with the onset of agriculture in the region, which would have created ideal conditions for the proliferation of malaria.”
Due to poor ancient DNA preservation in hot and humid climates, no ancient DNA from Arabia has been sequenced until now — preventing the direct examination of the genetic ancestry of its past populations.
Marc Haber, from the University of Birmingham Dubai, commented: “By obtaining the first ancient genomes from Eastern Arabia, we provide unprecedented insights into human history and disease progression in this region. This knowledge goes beyond historical understanding, providing predictive capabilities for disease susceptibility, spread, and treatment, thus promoting better health outcomes.”
“The rich population history of Bahrain, and more generally of Arabia, has been severely understudied from a genetic perspective. We provide the first genetic snapshot of past Arabian populations – obtaining important insights about malaria adaptation, which was historically endemic in the region,” commented Fatima Aloraifi, from the Mersey and West Lancashire NHS Trust.
Salman Almahari, Director of Antiquities and Museums at the Bahrain Authority for Culture and Antiquities, states, “Our study also paves the way for future research that will shed light on human population movements in Arabia and other regions with harsh climates where it is difficult to find well-preserved sources of DNA.”
Data gathered from the analysis of the four individuals’ remains allowed researchers to characterise the genetic composition of the region’s pre-Islamic inhabitants – insights that could only have been obtained by directly examining ancient DNA sequences.
Researchers collected ancient human remains from archaeological collections stored at the Bahrain National Museum, gathering DNA from 25 of them. Only four samples were sequenced to higher coverage due to poor preservation.
The finding of malaria adaptation agrees with archaeological and textual evidence that suggested malaria was historically endemic in Eastern Arabia, whilst the DNA ancestry of Tylos-period inhabitants of Bahrain corroborates archaeological evidence of interactions between Bahrain and neighbouring regions.
A report from the world’s leading scientific and medical experts on hormone-related health conditions raises new concerns about the profound threats to human health from endocrine disrupting chemicals (EDCs) that are ubiquitous in our surroundings and everyday lives.
The report, “Endocrine Disrupting Chemicals: Threats to Human Health” provides a comprehensive update on the state of the science around EDCs, with increasing evidence that this large group of toxic substances may be implicated in rising global health concerns.
The report from the Endocrine Society, co-produced with the International Pollutants Elimination Network (IPEN), includes detailed analyses on exposure to EDCs from four sources: plastics, pesticides, consumer products (including children’s products), and per-and polyfluoroalkyl substances (PFAS), a class of thousands of chemicals known or suspected to be EDCs.
The Endocrine Society-IPEN report is being released during the U.N. Environment Assembly (UNEA-6) meeting in Nairobi.
At UNEA key agenda items include welcoming the newly adopted Global Framework on Chemicals, advancing global action on highly hazardous pesticides, and threats to the circular economy from plastics and toxic chemicals.
The groups’ report anticipates an update from UNEP and the WHO expected later this year on their 2012 Report on State of the Science of Endocrine Disrupting Chemicals.
“A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions,” said the report’s lead author, Andrea C. Gore, PhD, of the University of Texas at Austin, and a member of the Endocrine Society’s Board of Directors.
“These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
By interfering with hormones and their actions, EDC exposure can impact many health-related functions, with consequences for increased risks of many serious conditions.
Evidence suggests that EDCs in the environment contribute to disorders such as diabetes, neurological disorders, reproductive disorders, inflammation, and compromised immune functioning.
Two of the four analyses in the report look at EDCs used in plastics and as pesticides.
Global production of plastics and pesticides is increasing even as scientists warn that chemical and plastic pollution is an escalating crisis. Glyphosate is the world’s most widely used herbicide, and a recent study found that glyphosate has eight of ten key characteristics of an EDC. Other studies have found links between glyphosate and adverse reproductive health outcomes.
Plastics are made with thousands of known toxic substances, some of which are known or suspected EDCs. The report examines bisphenols and phthalates, two toxic chemical groups found in many plastics. Exposures to EDCs from plastics occur at all phases of plastics production, use, disposal, and even from recycled plastics.
The Endocrine Society-IPEN report notes that, while evidence of health threats from EDCs is mounting, current regulations have not kept pace.
“EDCs are different than other toxic chemicals, but most regulations fail to address these differences,” said IPEN Science Advisor Sara Brosché, PhD. “For example, we know that even very low doses of endocrine disrupting chemicals can cause health problems and there may be no safe dose for exposure to EDCs. However, regulations typically do not protect against low-dose effects. We need a global approach to controlling EDCs based on the latest science with a goal of protecting the human right to a healthy environment.”
At the UNEA-6 meeting, IPEN is also releasing a new report on “The Global Threat from Highly Hazardous Pesticides,” highlighting ongoing health and environmental risks from HHPs, especially in low- and middle-income countries.
DDT, glyphosate, and chorpyrifos, three HHPs reviewed in the Endocrine Society report, are also highlighted in the new IPEN report as they continue to pose health threats especially in the Global South.
In addition to plastics and pesticides, the report looks at EDC exposures from arsenic and lead, and from widely used per- and polyfluoroalkyl substances (PFAS), humanmade “forever chemicals” used as oil and water repellents and coatings. Lead remains in use in paint in many countries, as documented in recent IPEN reports. Endocrine-related conditions from lead exposure may include delayed onset of puberty and early menopause. Arsenic is a common metal that has long been linked to cancer and other health conditions, and more recent evidence shows that arsenic can disrupt multiple endocrine systems. PFAS are used in hundreds of products including clothing and food packaging, but recent studies show that some PFAS can disrupt hormones such as oestrogen and testosterone and impair thyroid hormone functions.
Cedars-Sinai investigators have discovered why some injured kidneys heal while others develop scarring that can lead to kidney failure. Their findings, detailed in a paper published in the peer-reviewed journal Science, could lead to the development of noninvasive tests to detect kidney scarring and, eventually, new therapies to reverse the condition.
“The key to this discovery was our ability to directly compare injured kidney cells that successfully regenerated with those that did not,” said Sanjeev Kumar, MD, PhD, a nephrologist-scientist in the Board of Governors Regenerative Medicine Institute and the Department of Medicine at Cedars-Sinai and senior author of the study.
“Injured cells activate a protein called SOX9 to regenerate themselves. When they have healed, the cells silence this protein. Cells that aren’t able to regenerate leave SOX9 active, and this leads to a type of scarring called fibrosis. But when we deactivate SOX9 in a timely fashion, the scarring literally goes away.”
The kidneys can be injured by diabetes and high blood pressure, serious infections such as COVID-19, and overuse of antibiotics and non-steroidal anti-inflammatory pain medications, said Kumar, who is also part of the Department of Biomedical Sciences at Cedars-Sinai.
The SOX9 protein plays a major role in organ development but is not active in healthy adult kidneys.
In previous work at another institution, Kumar and team found that when kidneys are injured, the surviving cells reactivate SOX9 as part of the healing process.
In this study, Kumar and fellow investigators studied kidney damage in laboratory mice.
They labeled individual cells at the point of injury, then followed how the cells’ progeny evolved over time.
“At Day 10, some cells’ descendants were fully healed while others were not,” Kumar said.
“The cell lineage that healed had switched off SOX9 expression, while the unhealed lineage, in a continuing attempt to fully regenerate, maintained SOX9 activity. It’s like a sensor that switches on when cells want to regenerate, and off when they are restored, and we are the first to identify this.”
Further, investigators discovered that cells that were unable to regenerate began recruiting proteins called Wnts, another key player in organ development. Over time, this accumulation of Wnts triggered scarring. And they found that deactivating SOX9 a week after injury promoted kidney recovery.
Investigators observed the same process in patient databases from collaborating institutions in Switzerland and Belgium.
“We could see that by Day 7, human patients with transplanted kidneys that were slow to begin working also activated SOX9,” Kumar said.
“And in our collaborators’ database, we were able to distinguish that patients who had sustained SOX9 activation had lower kidney function and more scarring than those who did not. Human kidneys with cells that maintained SOX9 were also enriched with Wnts and showed increased fibrosis.”
These discoveries provide targets for drug development, as well as for noninvasive biomarker discovery permitting diagnosis of kidney fibrosis through the urine, Kumar said.
Currently, the only available test for kidney fibrosis is a biopsy, which carries many risks.
“Elucidating the mechanisms of scarless healing versus fibrosis has eluded investigators for decades and has implications beyond the kidney, including for certain cancers,” said Paul Noble, MD, chair of the Department of Medicine and director of the Women’s Guild Lung Institute at Cedars-Sinai and a co-author of the study.
