Colourised electron micrograph image of a macrophage. Credit: NIH
A new study reveals that immune cells in the liver react to high cholesterol levels and eat up excess cholesterol that can otherwise cause damage to arteries. The findings, published in Nature Cardiovascular Research, suggest that the response to the onset of atherosclerosis begins in the liver.
Immediate response from the liver
In the current study, researchers from Karolinska Institutet wanted to understand how different tissues in the body react to high levels of LDL, commonly called ‘bad cholesterol’, in the blood.
To test this, they created a system where they could quickly increase the cholesterol in the blood of mice.
“Essentially, we wanted to detonate a cholesterol bomb and see what happened next,” says Stephen Malin, lead author of the study and principal researcher at the Department of Medicine, Solna, Karolinska Institutet.
“We found that the liver responded almost immediately and removed some of the excess cholesterol.”
However, it wasn’t the typical liver cells that responded, but a type of immune cell called Kupffer cells that are known for recognising foreign or harmful substances and eating them up. The discovery made in mice was also validated in human tissue samples.
“We were surprised to see that the liver seems to be the first line of defence against excess cholesterol and that the Kupffer cells were the ones doing the job,” says Stephen Malin.
“This shows that the liver immune system is an active player in regulating cholesterol levels, and suggests that atherosclerosis is a systemic disease that affects multiple organs and not just the arteries.”
Several organs could be involved
The researchers hope that by understanding how the liver and other tissues communicate with each other after being exposed to high cholesterol, they can find new ways to prevent or treat cardiovascular and liver diseases.
“Our next step is to look at how other organs respond to excess cholesterol, and how they interact with the liver and the blood vessels in atherosclerosis,” says Stephen Malin. “This could help us develop more holistic and effective strategies to combat this common and deadly disease.”
University of Michigan researchers have identified the protein that enables mammals to sense cold, filling a long-standing knowledge gap in the field of sensory biology. The findings, published in Nature Neuroscience, could help unravel how we sense and suffer from cold temperature in the winter, and why some patients experience cold differently under particular disease conditions.
“The field started uncovering these temperature sensors over 20 years ago, with the discovery of a heat-sensing protein called TRPV1,” said neuroscientist Shawn Xu, a professor at the U-M Life Sciences Institute and a senior author of the new research.
“Various studies have found the proteins that sense hot, warm, even cool temperatures – but we’ve been unable to confirm what senses temperatures below about 60 degrees Fahrenheit (15.5°C).”
In a 2019 study, researchers in Xu’s lab discovered the first cold-sensing receptor protein in Caenorhabditis elegans, a species of millimetre-long worms that the lab studies as a model system for understanding sensory responses.
Because the gene that encodes the C. elegans protein is evolutionarily conserved across many species, including mice and humans, that finding provided a starting point for verifying the cold sensor in mammals: a protein called GluK2 (short for Glutamate ionotropic receptor kainate type subunit 2).
For this latest study, a team of researchers from the Life Sciences Institute and the U-M College of Literature, Science, and the Arts tested their hypothesis in mice that were missing the GluK2 gene, and thus could not produce any GluK2 proteins. Through a series of experiments to test the animals’ behavioural reactions to temperature and other mechanical stimuli, the team found that the mice responded normally to hot, warm and cool temperatures, but showed no response to noxious cold.
GluK2 is primarily found on neurons in the brain, where it receives chemical signals to facilitate communication between neurons. But it is also expressed in sensory neurons in the peripheral nervous system.
“We now know that this protein serves a totally different function in the peripheral nervous system, processing temperature cues instead of chemical signals to sense cold,” said Bo Duan, U-M associate professor of molecular, cellular, and developmental biology and co-senior author of the study.
While GluK2 is best known for its role in the brain, Xu speculates that this temperature-sensing role may have been one of the protein’s original purposes. The GluK2 gene has relatives across the evolutionary tree, going all the way back to single-cell bacteria.
“A bacterium has no brain, so why would it evolve a way to receive chemical signals from other neurons? But it would have great need to sense its environment, and perhaps both temperature and chemicals,” said Xu, who is also a professor of molecular and integrative physiology at the U-M Medical School. “So I think temperature sensing may be an ancient function, at least for some of these glutamate receptors, that was eventually co-opted as organisms evolved more complex nervous systems.”
In addition to filling a gap in the temperature-sensing puzzle, Xu believes the new finding could have implications for human health and well-being. Cancer patients receiving chemotherapy, for example, often experience painful reactions to cold.
“This discovery of GluK2 as a cold sensor in mammals opens new paths to better understand why humans experience painful reactions to cold, and even perhaps offers a potential therapeutic target for treating that pain in patients whose cold sensation is overstimulated,” Xu said.
Viral infections trigger more cases of intussusception in young children than previously thought, according to a new study. The research, led by Murdoch Children’s Research Institute (MCRI) and published in Clinical Infectious Diseases, found that during the COVID lockdowns, hospital admissions for intussusception, a medical emergency involving obstruction of the intestine, among young children significantly decreased.
For the study, 12 years of data was analysed across Victoria, NSW and Queensland. A total of 5589 intussusception cases were recorded between January, 2010 and April, 2022. Of those, 3179 were children under the age of two.
During the lockdown periods, Victoria and NSW experienced a decline in hospital admissions for intussusception among children under two by 62.7% and 40.1%, respectively. The rate of intussusception cases has now returned to normal levels.
MCRI and Monash University researcher Dr Ben Townley said the magnitude of the decline supported that common respiratory diseases such as colds, the flu and respiratory syncytial virus (RSV), were behind a significant proportion of intussusception cases.
“Reductions in intussusception hospital admissions were seen in all age groups, however most occurred in children less than two years of age,” he said.
“Intussusception is the leading cause of acute bowel obstruction in infants and young children and without prompt diagnosis and management, can be fatal.
“Countries with prolonged COVID lockdowns and suppression strategies saw reductions in common respiratory viruses, which influenced the drop in intussusception admissions.”
Victoria experienced the greatest lockdown duration, with Melbourne having six lockdown periods, for a total of 263 days. Greater Sydney had 159 days and Brisbane had 18 days in lockdown.
MCRI Professor Jim Buttery said the decrease in intussusception cases was greater than expected given previous research into the causes of the condition.
“Our analysis found commons viruses play a larger role than previously recognised in triggering intussusception,” he said.
Professor Buttery said the findings raised the possibility that emerging vaccines like the new RSV vaccines may help prevent intussusception.
“When a new vaccine against common childhood respiratory viruses is introduced, we may find there are some unexpected benefits, like protecting more children from intussusception,” he said.
Researchers from Sydney Children’s Hospital Network, University of Melbourne and Queensland Health also contributed to the findings.
Research into the link between disordered sleep and disease show an outsized burden on the most vulnerable. It’s sounding alarms for sleep equity to have a place on the public health agenda, reports Ufrieda Ho.
Scientists are increasingly connecting the dots on how a lack of sleep places a disproportionate health burden on at-risk population groups, including people living with HIV, women, informal workers, the elderly and the poor.
This year’s World Sleep Day on 15 March focuses on sleep equity. Researchers say that tackling sleep inequity and raising awareness for the importance of sleep as a pillar of good health could help stave off several looming public health pressures.
The lack of healthy sleep is linked to cardiovascular disease, obesity, hypertension, diabetes, mental health conditions and dementia. In South Africa, understanding the connection between sleep and HIV is also key to managing the health of the large ageing population of people living with the disease.
Karine Scheuermaier is associate professor at the Wits University Brain Function Research Group. The country’s oldest sleep laboratory founded in 1982 is based at the university’s medical school in Parktown, Johannesburg.
“Society understands the role of exercise and diet in good health but somehow sleep has not had the same kind of awareness or priority, even if sleep is linked to how well your body functions and your chances of developing disease,” she says. “We do everything else at the expense of sleep. Sleep is somehow a symbol of laziness in a work-driven society and we need to change this thinking.”
Sleep inequity in SA
Sleep inequity is linked to socio-economic realities, she says. Sleep inequity might affect the person who lives in an environment where safety and security is neglected or where there is a high threat of gender-based violence. It could also be having to navigate apartheid city planning that forced black people to live far from job hubs. This legacy means today many workers still wake up early to face long work commutes daily. There could also be inequity in division of labour in households, when one person wakes up to take care of children or elderly family members in the home.
Living in overcrowded informal settlements also presents disturbances for good sleep, including high levels of noise and bright floodlights as street lighting. Those who work in unregulated or informal sectors, including shift work or digital platform workers, like e-hailing drivers, are prone to lose out on quality sleep.
clinic that does clinical work, research, and training. Chandiwana says homing in on the intersection of HIV and sleep is critical in a South African context.
“The average person living with HIV who has started antiretroviral treatment on time should live as long as a person who doesn’t have HIV. But what we know is that the person with HIV is on average, living 16 years less of good health. They are more likely to develop type II diabetes, mental health issues, obesity, and heart disease – and we know poor sleep is linked to this,” she says.
Chandiwana says sleep science is still a relatively new field of medicine and the nascent research is still looking to better understand how sleep deprivation triggers immune pathways and chronic inflammation in people living with HIV, even those who are healthy and respond positively on treatment.
A current study at the clinic is looking into the intersection of obesity, sleep apnoea, and women living with HIV. Chandiwana says because so much is unknown, the issue of sleep equity extends to support and funding for more locally appropriate sleep research. Medical school curricula needs to change and more avenues to train people in sleep research needs to be established, she says.
“We have very little African data on sleep disorders and disordered sleep,” she says. She argues we need better data on things like how many people are affected by poor sleep, a better understanding of what is causing it and what it means, and then we need to present these findings to public health authorities to look at it as a public health issue.
“We do have specific challenges in our country. If you are trying to explain to someone, who isn’t South African, how the impact of load-shedding affects sleep or how living in a shack affects sleep, it’s not always easy to do,” she says.
Chandiwana says countries in the global North are already counting insufficient quality sleep as an economic cost measured in loss of productivity, efficiency, safety and society’s well-being. They are also changing public health policies accordingly. South Africa and the rest of the continent stand to be left behind, she says.
How to get better sleep in SA
Chandiwana says: “There is no lab in South Africa that does sleep studies for people in the public sector and no place in the public sector for people to even be diagnosed for a sleep disorder – so services are extremely limited. With something like sleep apnoea, we can’t offer patients in the public sector the gold standard intervention of CPAP [continuous positive airway pressure, which is a device of a face mask, a nose piece, and a hose that delivers a steady flow of air pressure to keep airways open while someone sleeps] because this is financially out of reach. Instead, we have to work with patients to help them lose weight and do positional therapy like training them to sleep on their backs.”
Other ways to get better sleep without costly intervention or sleeping tablets, the two scientists say, include getting exercise, not having food, stimulants or alcohol two to three hours before bedtime, limiting screen time of all kinds in the hour around bedtime, getting exposure to the early morning sunlight each day, keeping sleeping areas dark, quiet and at a comfortable temperature, and developing fixed sleep routines and sleep time rituals – like brushing your teeth, putting on pyjamas, reading for a short period and then going to sleep.
Ultimately, Chandiwana suggests it all comes back to building awareness that healthy sleep is part of health rights.
“We have to fight for sleep equity and we need people to know that sleep is not elitist – it’s not just reserved for some,” she says, “and we should not be accepting poor sleep as the norm”.
The News24 Business Awards – focused on areas such as costs, client service and claims – has named the largest self-administered medical scheme in SA as the nation’s best
Photo by National Cancer Institute on Unsplash
Bestmed Medical Scheme, the fourth largest open medical scheme and the largest self-administered medical scheme in the country, has been honoured with the News24 Medical Scheme of the Year award, at the 2024 News24 Business Awards.
These awards recognise client satisfaction scores surveyed from more than 4 000 subscribers, along with their assessment of the offering, among other criteria, and cover multiple sectors, including banking, insurance, and healthcare.
Focused on a range of criteria, including customers’ satisfaction with key issues like costs, and client service and claims, the awards also consider the company’s transparency / communication with clients, overall contribution to South Africa, shareholder value creation and business performance. These elements are also evaluated by News24’s financial reporters, as well as fund managers and analysts – with results ultimately audited by an actuarial consultant.
This year, Bestmed took the coveted Medical Scheme Award notably because of the outstanding feedback from its clients in a survey of thousands of News24 readers, especially when it came to its claim process and communication. News24 journalists also gave Bestmed a very high score for how easy it is to understand what is covered and for value for money.
“Bestmed is truly proud to be named Medical Scheme of the Year, particularly based on criteria that are so client-focused,” says Leo Dlamini, CEO and Principal Officer of Bestmed Medical Scheme. “These awards celebrate the best in corporate South Africa, and we are pleased to have been recognised for our efforts in this space. We have always believed in great member experience, value for money offerings and making a difference in the communities in which we operate.”
Awards of this nature are nothing new to the Scheme, which has received many similar accolades in recent years. Bestmed was voted, for a second successive time, as the leader in the South African medical scheme industry when it comes to customer satisfaction, according to the most recent SA Customer Satisfaction Index (SA-csi). Last year, Bestmed also received the Board of Health Funders’ Titanium Award for Excellence in Creating Access to Quality Healthcare – this, for the third consecutive time. Bestmed was also voted first in 2020 and 2022, and second in 2023, for customer experience in the Ask Afrika Orange Index® benchmark’s medical aid category.
“Members are at the centre of everything that we do. Our ‘Personally Yours’ promise is a commitment to consistently providing our members with the highest quality service, while also offering value for money. This award affirms our conviction and energises us to maintain the focus on member experience and value-for-money offerings. This will continue to set Bestmed apart as a healthcare funder of choice,” concludes Dlamini.
About Bestmed
Bestmed Medical Scheme is the largest self-administered medical scheme in South Africa. Bestmed’s “Personally Yours” philosophy leads the way in the medical aid industry. Bestmed’s membership offerings include 14 unique plans, designed to suit the needs of members. Beneficiaries have access to a network of more than 18 000 healthcare professionals countrywide. The Scheme’s head office is based in Tshwane (Gauteng). Bestmed has satellite offices in Nelspruit, Durban, Cape Town, Gqeberha (Port Elizabeth) and Polokwane. For more information visit www.bestmed.co.za
Space travel and zero gravity can take a toll on the body. A new study has found that astronauts with no prior history of headaches may experience migraine and tension-type headaches during long-haul space flight, which includes more than 10 days in space. Studying this type of headache may provide new insights into the mechanisms behind headaches on Earth. The study was published in Neurology.
“Changes in gravity caused by space flight affect the function of many parts of the body, including the brain,” said study author W. P. J. van Oosterhout, MD, PhD, of Leiden University Medical Center in the Netherlands.
“The vestibular system, which affects balance and posture, has to adapt to the conflict between the signals it is expecting to receive and the actual signals it receives in the absence of normal gravity. This can lead to space motion sickness in the first week, of which headache is the most frequently reported symptom. Our study shows that headaches also occur later in space flight and could be related to an increase in pressure within the skull.”
The study involved 24 astronauts from the European Space Agency, the U.S. National Aeronautics and Space Administration (NASA) and the Japan Aerospace Exploration Agency. They were assigned to International Space Station expeditions for up to 26 weeks from November 2011 to June 2018.
Prior to the study, nine astronauts reported never having any headaches and three had a headache that interfered with daily activities in the last year.
None of them had a history of recurrent headaches or had ever been diagnosed with migraine.
Of the total participants, 22 astronauts experienced one or more episode of headache during a total of 3596 days in space for all participants. Astronauts completed health screenings and a questionnaire about their headache history before the flight.
During space flight, astronauts filled out a daily questionnaire for the first seven days and a weekly questionnaire each following week throughout their stay in the space station.
The astronauts reported 378 headaches in flight. Researchers found that 92% of astronauts experienced headaches during flight compared to just 38% of them experiencing headaches prior to flight.
Of the total headaches, 170, or 90%, were tension-type headache and 19, or 10%, were migraine. Researchers also found that headaches were of a higher intensity and more likely to be migraine-like during the first week of space flight.
During this time, 21 astronauts had one or more headaches for a total of 51 headaches – of which 39 were considered tension-type headaches and 12 were migraine-like or probable migraine.
In the three months after return to Earth, none of the astronauts reported any headaches.
“Further research is needed to unravel the underlying causes of space headache and explore how such discoveries may provide insights into headaches occurring on Earth,” said Van Oosterhout.
“Also, more effective therapies need to be developed to combat space headaches as for many astronauts this a major problem during space flights.”
This research does not prove that going into space causes headaches; it only shows an association.
A limitation of the study was that astronauts reported their own symptoms, so they may not have remembered all the information accurately.
While three new tuberculosis (TB) medicines have been registered in South Africa over the last decade, TB treatment still comes with several side effects and requires taking multiple different medicines, typically for six or more months. The search for better TB medicines got a boost last week with the presentation of promising findings from a study conducted in South Africa on an experimental drug called quabodepistat. Elri Voigt reports on this and other TB studies presented at a conference in Denver, Colorado.
Arguably, the biggest TB news at the Conference on Retroviruses and Opportunistic Infections (CROI) this year was that the experimental new TB drug quabodepistat performed well in a phase 2b/c clinical trial. This means the drug can now proceed to a pivotal phase 3 trial (medicines are typically approved by regulators only after positive results in phase 3 trials).
The interim study results presented at CROI indicated that quabodepistat in combination with bedaquiline and delamanid and given for four months to people with drug susceptible TB is safe and efficacious, when compared to the six-month standard of care regimen. The standard of care regimen, currently used in South Africa’s public sector, consists of the drugs rifampicin, isoniazid, ethambutol, and pyrazinamide.
Participants were split into four study arms to either receive 10mg, 30mg or 90mg of quabodepistat (along with delamanid and bedaquline) once a day for four months or the standard of care regimen for six months. In the quabodepistat arms, a total of 98 study participants completed treatment, compared to 19 in the standard of care arm.
Taken together, 96% of participants in the quabodepistat arms had sputum culture conversion compared to 91% in the standard of care arm. Sputum culture conversion means TB was no longer detected in sputum samples that people coughed up when those samples were grown in the lab.
The study was conducted at several sites in South Africa and was funded by the Japanese pharmaceutical company Otsuka.
‘Furthest along’
Lindsay McKenna, the TB Project Co-Director at Treatment Action Group (TAG – a New York-based NGO), explained to Spotlight that quabodepistat is a new drug with a new mechanism of action for inhibiting TB’s cell wall synthesis. Essentially, this means that the drug interferes with the TB bacteria’s cell wall structure.
While there are a few new drugs that work the same way, quabodepistat is the furthest along.
“It’s the first in a new class of TB drugs to reach this stage since bedaquiline and delamanid were in phase 2b over ten years ago,” McKenna said.
There is however still some way to go before we will know if quabodepistat is bound for wider use than just in clinical trials. “We need to see data on clinical outcomes first,” McKenna told Spotlight, adding that quabodepistat is also being assessed in another ongoing phase 2b/c clinical trial.
“Remember that we have only seen sputum culture conversion results. Follow up is ongoing and so we will learn more when we see the proportion of participants with favorable outcomes (for example relapse free cure) 12 months post randomisation,” she said. “In the meantime, I think Otsuka should immediately begin working to start up a pre-approval access programme to enable people with unmet needs to access quabodepistat.”
Safety signals
Dr Simbarashe Takuva, Associate Director of Clinical Development at Otsuka Novel Products GmbH (an affiliate of Otsuka), who presented the results on behalf of the study team, said that overall, the quabodepistat regimen was well tolerated and considered safe.
In terms of side effects, the adverse events reported were generally described as mild or moderate, but there were some concerning signals. Grade 3 adverse events stood at 15% in the quabodepistat 10mg arm, 12% in the 30mg arm, 11% in the 90mg arm and 5% in the standard of care arm. Grade 3 adverse events are typically serious enough to prevent someone from working.
Takuva said that there were no serious adverse events (which we understand to mean grade 4/life threatening adverse events) related to the study drugs. There were also no treatment discontinuations related to the drugs. There was a single death in the study, a 25-year-old man who had met all study eligibility criteria but got sicker during the study. The study drugs were halted and standard of care drugs were given instead but the participant later died in hospital.
The researchers also looked for signs that quabodepistat might adversely affect the liver and the heart, but no safety signals related to the drugs were seen in either the liver (hepatoxicity) or the heart (cardiotoxicity).
“The data presented didn’t raise concerns about any treatment related cardio- or hepatotoxicity signals, however, it was a relatively small study, and the inclusion criteria were conservative,” McKenna commented on these findings.
One snag is that the results presented at CROI did not provide a clear answer regarding which of the three quabodepistat dosages in the study is preferable. Based on the clinical data, Takuva said it is difficult to determine which dose is best to use. He did however point out that additional work is being done looking at Pharmacokinetic and Pharmacodynamic data which will hopefully help provide more information on the ideal dose.
“Follow up on this study is ongoing. We await the final results of our phase 2 trial toward the end of the year,” he told Spotlight.
No study participants with HIV
One big limitation of these results is that the study did not enroll any people living with HIV. According to Takuva, the study had a strict exclusion criterion for the CD4 count of enrolling anyone living with HIV. A person’s CD4 count is a measure of the state of one’s immune system – higher counts are better.
Initially, the CD4 count cut off for the study was set at above 500 cells/mm3, then was amended to 350 cells/mm3 and finally it was dropped to above 250 cells/mm3 but by that time it was too late to enroll anyone living with HIV.
“The interim results are encouraging. However, I was really surprised and disappointed that they weren’t able to enroll any people living with HIV in the trial,” McKenna told Spotlight.
When asked about this, Takuva told Spotlight that the protocol did include the provision to recruit people living with HIV, but it was not feasible to include any. However, people living with HIV will be considered as important to include in any phase 3 trials going forward.
“As with all studies, we need to balance patient safety and the goal of the study outcome. In this instance, despite our best efforts, recruitment of people living with HIV was not feasible, though as we consider the possibility of a phase 3 trial, people living with HIV will remain a population that we consider important to include as far as possible in the phase 3 trial,” he said.
Treating DR-TB in people living with HIV
In contrast to the lack of people with HIV in the quabodepistat study, research was also presented at CROI looking specifically at how people living with HIV did in the landmark endTB trial. Other results from endTB were previously reported and the trial is widely considered one of a hand full of key trials transforming the treatment of drug-resistant forms of TB. The researchers found that two nine-month regimens studied in endTB did particularly well in people living with HIV. Such findings are of particular importance in a country like South Africa where many people who fall ill with TB are also living with HIV. (For those interested in the details, the two regimens were bedaquiline/linezolid/moxifloxacin/pyrazinamide and bedaquiline/clofazimine/linezolid/levofloxacin/pyrazinamide)
Some disappointments
Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash
In a disappointing development, researchers presenting at CROI reported that a study testing a three-month regimen for the treatment of drug-susceptible TB was stopped early after an interim review found the regimen had poor efficacy compared to the six-month standard of care. The regimen contained the drugs clofazimine and rifapentine, among others. It means that for now the shortest regimen for treating drug-susceptible TB validated in a clinical trial remains a four-month regimen containing the medicines rifapentine and moxifloxacin, among others. That four-month regimen is not yet in wide use, even though findings confirming its safety and efficacy were reported in 2020.
We also received some bad news on an experimental TB vaccine called H56:IC31. The idea of H56:IC31 was to vaccinate people who were just cured of TB to prevent the TB from coming back – people whose TB is deemed to be cured are known to have an increased risk of falling ill with TB again. Despite promising signs in earlier studies, the vaccine failed to reduce TB recurrence in a phase 2 clinical trial of over 800 people. Much of this study was conducted at sites in South Africa.
TB treatment’s impact on mental and physical health
Another interesting study conducted in South Africa and presented at CROI looked at the changes in mental and physical health that people ill with TB experience before and after treatment. It found that the quality of life and physical fitness of participants was reduced at the start of TB treatment but did improve by the end of TB treatment.
The researchers looked at 200 study participants split between South Africa, Zambia, Malawi, Mozambique and Zimbabwe. Their mental and physical health was assessed when they started TB treatment through a standardised short form quality of life survey, depression assessed through a patient health questionnaire and their physical health was tested using a six-minute walk test. Participants were assessed again when treatment was completed, and data was compared to see what changed between the start and end of TB treatment.
Overall, participant’s physical quality of life increased by 39% by the end of TB treatment, mental quality of life increased by 19%, ability to do a six-minute walk increased by 15% and depression scores decreased by 26%.
Long-acting therapies for TB
Long-acting therapies have been making waves for some time in HIV treatment and a long-acting injection and ring are currently being offered in pilot projects in South Africa. Two studies of long-acting therapies in mice presented at CROI show that there is at least some movement in this area as well when it comes to TB. Such long-acting therapies have particular potential for TB preventive therapy – with for example what is now a three-month course of pills being administered as a single long-acting injection.
One study found that a long-acting injectable form of the drug rifapentine had similar efficacy to a one-month course of preventive therapy in pill form, while another had similarly promising findings for an injection using a long-acting formulation of a diarylquinoline (a class of TB drugs that include bedaquiline). It is anticipated these early proof of concept mouse studies will be followed by studies in humans.
A person’s age, sex and location are correlated with the chance that they have a bloodstream infection that is resistant to antibiotics, according to a new study published March 14th in PLOS Medicineby Gwenan Knight of the London School of Hygiene and Tropical Medicine, UK, and colleagues.
Antimicrobial resistance (AMR), in which infections cannot be treated with antibiotics, is a major global public health threat.
Little has been known about how the prevalence of resistance varies with age and sex even though antibiotic usage, changes in immune function, and exposure to high-risk settings are all linked to age and sex.
In the new study, researchers analyzed data collected as part of routine surveillance between 2015 and 2019 on bloodstream infections in 944,520 individuals across 29 European countries.
The team looked at which bacterial species were isolated and sent to the surveillance service, and which antibiotics were used to treat the infections.
Distinct patterns in resistance prevalence by age were observed throughout Europe but varied across bacterial species.
For most but not all bacteria, peaks in resistance were seen at the youngest and oldest ages.
The occurrence of methicillin-resistant Staphylococcus aureus (MRSA) increased with age and the occurrence of aminopenicillin resistance in Escherichia coli decreased with age.
Some antimicrobial resistance profiles peaked in middle-age; Pseudomonas aeruginosa was most likely to be resistant to several antibiotics around 30 years of age and, for women, the incidence of bloodstream infections due to E. coli peaked between ages 15 and 40. There were other important differences between sexes; in general, men had a higher risk of antimicrobial resistance than women.
“These findings highlight important gaps in our knowledge of the epidemiology of antimicrobial resistance that are difficult to explain through known patterns of antibiotic exposure and healthcare contact,” the authors say.
“Our findings suggest that there may be value in considering interventions to reduce antimicrobial resistance burden that take into account important variations in antimicrobial resistance prevalence with age and sex.”
The authors add, “Our findings, that the prevalence of resistance in bloodstream infections across Europe varies substantially by age and sex, highlights important gaps in our knowledge of the spread and selection of AMR. In order for us to address this growing threat to public health, we now need data from a wider range of sources to determine the contribution that cultural versus natural history differences have in driving these patterns globally and the role that they play in the increasing rates of AMR being seen.”
Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. Study findings were published in the journal Immunity.
Approximately 95% of the world’s population is infected with EBV, which remains in the body permanently, typically in B lymphocytes, which are antibody-producing immune system cells, and cells lining the throat and pharynx.
EBV can sometimes lead to B-cell cancers, including Burkitt, Hodgkin and non-Hodgkin lymphomas, or to gastric or nasopharyngeal cancers.
Recently, EBV infection was shown to significantly raise the risk of developing multiple sclerosis.
There is no vaccine to prevent EBV infection nor a specific treatment.
In this study, investigators examined a viral protein called gp42, which the virus must use to infect B cells. The research was led by Jeffrey I. Cohen, M.D., and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Theoretically, a vaccine or antibody-based treatment capable of blocking gp42’s ability to bind to or fuse with B cells would prevent EBV infection and, thus, the virus’s ability to persist in those cells.
The team generated two gp42-specific mAbs, A10 and 4C12, and used X-ray crystallography to visualize how they interacted with gp42.
The crystal structures revealed that the two mAbs interacted with distinct, non-overlapping sites on gp42.
Monoclonal antibody A10 blocked the site on gp42 required for receptor binding, while 4C12 interfered with a different site that is involved in membrane fusion.
Next, the scientists tested A10, 4C12 and several other mAbs in mice for their ability to prevent EBV infection and EBV lymphomas.
The mAb A10 provided nearly complete protection against EBV infection and none of the mice developed lymphoproliferative disease or lymphoma.
In contrast, nearly all the mice treated with other mAbs became infected and some developed lymphoproliferative disease or lymphoma.
If future studies show mAb A10 to be safe and effective in humans, it could have clinical applications, particularly in people who have not been infected with EBV; those with immunodeficiency conditions, including severe combined immunodeficiency; or people receiving transplants.
People with such conditions are at risk of developing severe or fatal cases of EBV disease during their initial encounter with the virus.
The investigational monoclonal antibody could potentially be used prophylactically to prevent or better control EBV infections in such cases, the investigators note.
Additionally, the study team suggests that identification of the vulnerable sites on gp42 also paves the way to designing future vaccines that could elicit antibodies against one or both of the newly described sites.
An enthusiastic response to food in early childhood may be linked to a higher likelihood of experiencing eating disorder symptoms in adolescence, according to a new study led by researchers at UCL and Erasmus University Rotterdam.
The study, published in The Lancet Child & Adolescent Health, looked at survey data from 3670 young people in the UK and the Netherlands to investigate how appetite traits in early childhood might relate to the likelihood of developing eating disorder symptoms up to 10 years later.
The team also found that a slower pace of eating and feeling full more quickly (high sensitivity to satiety) in early childhood may be protective against developing some eating disorder symptoms later.
Co-lead author Dr Ivonne Derks (UCL Institute of Epidemiology & Health Care) said: “Although our study cannot prove causality, our findings suggest food cue responsiveness may be one predisposing risk factor for the onset of eating disorder symptoms in adolescence.
“However, high responsiveness to food is also a normal and very common behaviour and should be seen as just one potential risk factor among many rather than something to cause parents worry.”
Higher food responsiveness was linked to a 16% to 47% increase in the odds of reporting eating disorder symptoms, including binge eating symptoms, uncontrolled eating, emotional eating, restrained eating and compensatory behaviours.
The 47% increase was found for binge eating symptoms (eating a very large amount of food and/or experiencing the feeling of loss of control over eating), meaning that adolescents whose parents rated them highest on food responsiveness were almost three times more likely to report binge eating symptoms compared to adolescents whose parents scored them lowest.
A 16% increase in odds was found for restrained eating, whereby a person restricts their intake of food to lose weight or avoid weight gain.
Just like food responsiveness, emotional overeating in early childhood was also linked with higher odds of engaging in compensatory behaviours, which are intended to avoid weight gain, such as skipping meals, fasting and excessive exercise.
In turn, some appetite traits seemed to be protective against developing eating disorder symptoms later. Higher satiety responsiveness – that is, feeling full more quickly after eating, and feeling full for longer – was linked to lower odds of uncontrolled eating (defined as the extent to which someone feels out of control and eats more than usual) and compensatory behaviours.
A slower pace of eating, meanwhile, was linked to lower odds of compensatory behaviours and restrained eating.
The researchers also found that appetite traits such as food fussiness, emotional undereating (eating less due to low mood), and enjoyment of food in early childhood were not linked to later eating disorder symptoms in adolescence.
For the study, the researchers looked at data from two separate longitudinal studies: Generation R, following children born in Rotterdam, the Netherlands, between 2002 and 2006, and Gemini, which follows twins born in England and Wales in 2007.
Appetite traits were assessed based on parents’ questionnaire responses when the children were aged four or five. Eating disorder symptoms were self-reported by the then adolescents themselves at ages 12 to 14, when eating disorder symptoms typically start to emerge.
About 10% of the adolescents reported binge eating symptoms, where people eat an unusual amount of food and/or experience the feeling of loss of control over eating. Next to that, 50% reported at least one behaviour to compensate their food intake or to avoid gaining weight, such as skipping a meal.
Co-senior author Dr Clare Llewellyn (UCL Institute of Epidemiology & Health Care) said: “While the role of appetite in the development of obesity has been studied for many decades, this is the first study to comprehensively examine the role of appetite traits in the development of eating disorder symptoms.
“Eating disorders can be harder to treat effectively once they develop and so it would be better to prevent them from occurring in the first place. Our work in identifying risk factors in early life aims to support the development of possible prevention strategies. These could, for instance, involve providing extra support to children at higher risk.”
Appetite traits are divided into food approach appetitive traits (eg, food responsiveness, enjoyment of food, emotional overeating) and food avoidance traits (eg, satiety responsiveness, food fussiness, slowness in eating, emotional undereating).
The researchers found that non-responsive feeding practices, such as putting pressure on children to eat or using food as a reward or to soothe emotions, were linked to a higher likelihood of specific eating disorder symptoms later. However, the associations were small and varied between the two cohorts, and the researchers said further replication studies were needed.
