Sudy finds early treatment was associated with a 31% lower likelihood of ICU admission
Photo by Andrea Piacquadio on Unsplash
A new US study finds antiviral treatment is linked to fewer intensive care unit (ICU) admissions and shorter hospital stays for children hospitalised with influenza. The study, published in JAMA Pediatrics and led by experts at the University of Colorado Anschutz, is one of the most comprehensive real-world evaluations of antiviral treatment in paediatric influenza to date.
The research found that children who received early treatment with antiviral treatment, in this case oseltamivir, were 31% less likely to be admitted to an ICU and had shorter hospital stays than those who did not receive the antiviral.
The findings come as use of antiviral medications among hospitalised children with influenza has declined despite national guidelines recommending treatment for suspected or confirmed cases.
“After one of the most severe influenza seasons in the past two decades, these findings reinforce the importance of treating children with influenza who are hospitalised. Our findings show that oseltamivir treatment can decrease the risk of needing critical care, even if started beyond the first two days of the start of the illness,” said the paper’s senior author Suchitra Rao, MD, professor in the department of paediatrics at the University of Colorado Anschutz School of Medicine and infectious disease specialist at Children’s Hospital Colorado.
One of the largest and most rigorous real-world evaluations
The researchers looked at data from more than 7000 paediatric hospitalisations captured through a FluSurv-NET, a CDC-supported surveillance network that captures laboratory-confirmed influenza hospitalisations. The data spanned 13 states and eight influenza seasons.
Unlike many earlier observational studies, this research accounted for when symptoms began and when antiviral treatment started, providing stronger real-world evidence on the effectiveness of oseltamivir in hospitalised children.
“Earlier studies were often missing key information about when children became sick or whether they started antiviral treatment before being hospitalised, making it harder to evaluate the medication’s effectiveness. By capturing those details and using advanced statistical methods, we were able to produce stronger real-world evidence to inform the care of children hospitalised with influenza,” adds Rao.
The findings reinforce current national recommendations that children hospitalised with suspected or confirmed influenza receive an antiviral medication as soon as possible.
Children hospitalised with severe pneumonia can safely switch from injectable to oral antibiotics once they begin to recover, allowing many to return home sooner and complete treatment outside hospital, according to a major clinical trial involving 13 hospitals in Southern Africa.
The new results were published in The Lancet. The trial involved partners across Europe and Africa and was led with researchers at City St George’s, University of London.
Pneumonia remains one of the leading infectious killers of children worldwide, particularly in low- and middle-income countries. Current World Health Organization (WHO) guidelines recommend five days of injectable antibiotics for children hospitalised with severe community-acquired pneumonia, often requiring them to stay in hospital even after they have already substantially improved.
Longer hospital stays are more expensive, placing a higher burden on already pressurised healthcare systems and facilities, whilst increasing the risk of hospital-acquired antibiotic-resistant infections and impacting the wellbeing of the children and their families.
The PediCAP trial is one of the largest studies to assess antibiotic treatment for severe childhood pneumonia in Africa. The study enrolled 1101 children aged two months to six years with community-acquired pneumonia that developed outside hospital but was severe enough to require hospital treatment. Thirteen hospitals across South Africa, Uganda, Zambia, Zimbabwe and Mozambique contributed to the study.
All children in the trial began treatment with a WHO-recommended injectable antibiotic. Some were assigned to switch to either oral amoxicillin or oral amoxicillin-clavulanate when their condition had improved, as confirmed by a healthcare worker. Researchers compared these children to those who received the WHO-recommended injectable treatment for the full five days.
Children who switched to oral antibiotics recovered just as well as those who remained on injectable treatment for five days. Rates of hospital readmission or death within 28 days were similar across all groups – 6% for oral amoxicillin, 7% for oral amoxicillin-clavulanate and 6% for injectable antibiotics – showing that an early switch to oral treatment is a safe and effective strategy.
The standard amoxicillin performed just as well as the broader-spectrum antibiotic amoxicillin-clavulanate, supporting the use of a treatment that is cheaper and widely available.
Researchers also compared how well children recovered with different durations of antibiotic treatment, ranging from four to eight days in total. A total antibiotic course of four to five days was as effective as longer courses of seven or eight days, suggesting many children can be treated successfully with substantially less antibiotic exposure than is often used in practice.
Children who switched to oral antibiotics left hospital around one day earlier compared to those who remained on injectable treatment for the full five days.
Co-lead author Dr Michelle Clements, based at UCL Innovative Clinical Trials Unit, said: “PediCAP is the first large-scale study to use an innovative multi-arm trial design, which we developed here at UCL, to evaluate different antibiotics and treatment durations at the same time. Rather than simply comparing one short course with one longer course, this approach allowed us to establish that the shortest studied treatment strategy was effective and safe, while also helping us to understanding the relationship between treatment length and effect.
“By generating robust evidence more efficiently, this trial design has helped answer questions that we hope will support changes to global treatment guidelines and improve care for millions of children with pneumonia worldwide.”
Co-lead author Professor Julia Bielicki, from City St George’s, University of London, said: “Every year millions of children around the world are admitted to hospital with severe pneumonia. Our study shows that once a child is clinically improving, it is safe to switch from injectable to oral antibiotics, and complete treatment at home.
“This simple change could help children get back to their families sooner, reduce pressure on busy hospitals, lower healthcare costs and avoid sometimes catastrophic financial impacts on families from lost caregiver earnings. Because amoxicillin is affordable and widely available, these findings have the potential to change clinical practice and improve care for children around the world.”
The trial was funded by the European Union’s EDCTP2 programme and sponsored by the Penta Foundation.
Chinese researchers have revealed the key role of iron in initiating allergic airway inflammation. The study, which was published in Cell, was conducted by a team led by Prof SUN Bing from the Center for Excellence in Molecular Cell Science (Shanghai Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences (CAS), along with Prof LIU Xing’s team from the Shanghai Institute of Materia and Medica of CAS.
The research showed that environmental allergens can use an iron-dependent mechanism to activate gasdermin D (GSDMD) in airway epithelial cells, thereby promoting IL-33 release and initiating allergic airway inflammation – the main pathological basis for the onset and progression of asthma.
When environmental allergens such as pollen, house dust mites, and fungal proteases enter the airway, they act on lung epithelial cells and induce the release of alarmins, including IL-33. IL-33 then activates type 2 innate lymphoid cells (ILC2s), leading to eosinophil infiltration, mucus production, and airway tissue damage.
Previous studies have shown that GSDMD is involved in IL-33 release, but how allergens activate GSDMD had remained unclear. In this study, the researchers found that allergen stimulation rapidly increased the labile iron pool in airway epithelial cells, and GSDMD was cleaved and activated through a mechanism independent of conventional proteases.
Using mouse models induced by papain or house dust mites, the researchers observed a rapid rise in lung iron levels after allergen challenge, occurring in parallel with IL-33 release. Treatment with an iron chelator markedly inhibited GSDMD cleavage and IL-33 release, whereas iron supplementation enhanced these responses. This iron-driven effect was largely abolished in GSDMD-deficient mice, indicating that the pro-inflammatory activity of iron is highly dependent on GSDMD.
Furthermore, the researchers showed that cell-surface protease-activated receptor PAR1 serves as an important entry point for allergen sensing. Papain directly cleaves PAR1, which in turn initiates NCOA4-mediated ferritinophagy and releases additional free iron. The iron chaperone PCBP2 delivers iron to the vicinity of GSDMD, where the E309/Q312 residues of GSDMD are responsible for iron binding. When these sites are mutated, GSDMD can no longer be efficiently cleaved or mediate IL-33 release.
The researchers found that this cleavage process does not depend on canonical inflammasome-associated caspases. Instead, iron delivered by PCBP2 locally triggers a Fenton reaction, generating short-range hydroxyl radicals that drive oxidative cleavage of GSDMD.
In vivo experiments showed that pretreatment with the iron chelator DFP significantly alleviates papain-induced airway inflammation, reducing eosinophil infiltration, IL-5 and IL-13 levels, and mucus secretion. Conversely, iron supplementation aggravated inflammatory responses in wild-type mice, but failed to produce the same effect in GSDMD-deficient mice.
These findings establish the iron–GSDMD–IL-33 axis as an important driver of allergen-induced type 2 immune responses, and suggest that PAR1, iron mobilisation, PCBP2, and local iron-mediated reactions may represent potential intervention points for asthma and other allergic diseases.
In summary, this study proposes a new mechanism for the initiation of allergic airway inflammation. It expands the understanding of GSDMD activation and immunological functions of iron metabolism, and provides new insight into the prevention and treatment of asthma and related allergic diseases.
Study links shifts to buildup of susceptible hosts, explores similar shifts in heart-related deaths
Creative layout featuring scientifically-based 3D renderings of respiratory syncytial virus (RSV). RSV is a common contagious virus that infects the human respiratory tract. Credit: NIAID
A German analysis explores what underlies shifts in the timing of seasonal surges of respiratory diseases, as well as shifts in surges of heart-related deaths, that occurred after the COVID-19 pandemic began. Michael Sieber and Arne Traulsen of the Max Planck Institute for Evolutionary Biology, Germany, present these findings in the open-access journal PLOS Global Public Health on July 15, 2026.
Rates of respiratory infections such as the flu and RSV typically peak during seasons when transmission rates rise. Rates of death from any cause – not just from infection – follow a similar seasonal pattern.
However, the drivers underlying the exact timing of these surges have been unclear. The COVID-19 pandemic provided a unique opportunity to explore these dynamics, since interventions like social distancing and masking disrupted typical transmission patterns of other respiratory diseases. Sieber and Traulsen analysed data on weekly respiratory infection rates and death rates in Germany, covering the last 14 years.
The analysis showed that, pre-pandemic, respiratory infections almost always surged for a few weeks February and March. After the pandemic began, intervention efforts tamped down infections, eliminating one seasonal surge. Once infections rose again, surges shifted to December or earlier. Now, these peak weeks are gradually resuming pre-pandemic timing.
Using well-established epidemiological modelling tools, the researchers found that population-level loss of immunity after the skipped seasonal surge led to buildup of susceptible hosts, resulting in higher transmission earlier in the season. That is, seasonal transmission variations present a window of opportunity for a surge, and the size of the pool of susceptible hosts at the start of that window determines when, exactly, the surge occurs.
Similarly, typical seasonal surges in rates of death from any cause – but particularly from cardiovascular disease – also shifted earlier post-pandemic. Thus, respiratory infections may be key drivers of the timing of seasonal surges in cardiovascular deaths. More research is needed to explore this connection, but it aligns with other evidence that respiratory infections are a significant risk factor for cardiovascular disease.
On the basis of their findings, the researchers emphasize the importance of monitoring people’s infection history and improving vaccination coverage.
The authors add: “News stories of an earlier than usual onset of the flu season during the COVID-19 pandemic motivated us to look into the available epidemiological data more closely. We were surprised by the magnitude of the shift in timing of seasonal respiratory infections in Germany, and interested in trying to predict if this would turn out to be a long-term effect of the pandemic or if we should expect a quick return to the normal seasonal timing. The most recent flu seasons confirmed that the seasonal timing indeed shifts back to normal within one or two seasons, most likely due to a return to the pre-pandemic population-levels of immunity to the most common respiratory pathogens. We were even more surprised to see that the seasonal dynamics of all-cause mortality, which is dominated by cardiovascular diseases, closely followed the shift in timing of respiratory infections. This adds to the growing evidence that respiratory infections are an important risk factor for cardiovascular problems.”
Future therapies for respiratory syncytial virus (RSV) must target both the virus and its immune response to ensure babies get the best possible outcomes, finds a new study by researchers at UCL and Great Ormond Street Hospital for Children (GOSH).
RSV is the biggest cause of serious illness in babies, with over three million hospital admissions worldwide because of the virus every year. It causes wheezing and breathing difficulties, and in the worst cases babies end up in intensive care. Despite this, treatment options for infants who develop severe disease remain extremely limited.
As part of the new study, published in Nature Communications and funded by Animal Free Research UK and UK Research and Innovation (UKRI), researchers built a new lab model of baby lungs to show why RSV makes infants so much sicker than adults and allow them to test new treatments before they reach patients.
The miniature model of a baby’s airways was created using real infant airway cells, blood vessel cells and neutrophils (a type of white blood cell that acts as the immune system’s primary response to infection).
To compare with an adult response to RSV, the research team also made a model of an adult’s airways.
Dr Claire Smith (UCL Great Ormond Street Institute of Child Health), who led the study, said: “This model allows us to watch early immune responses unfold and study them in a human setting that reflects the infant airway. That’s something animal models often struggle to capture, especially when it comes to age-specific effects.”
When the models were infected with RSV, the team found that baby airway cells attracted far more white blood cells than adult airway cells did. This influx can block babies’ small airways and make it harder for them to breathe.
Neutrophils normally circulate in the blood but enter lung tissue in response to infection. In the baby airway model, researchers found that the neutrophils that entered the lung tissue were more activated and triggered a stronger inflammatory reaction than in the adult model.
This effect depended on the immune cells physically moving through the infected tissue, not just responding to chemical signals released by it, making this type of model essential for studying it.
This suggests it’s the infant airway itself, not just the virus, that ramps up the immune response and causes damage to the lungs.
First author, Dr Machaela Palor (UCL Great Ormond Street Institute of Child Health), said: “These findings help explain why RSV is often much more severe in infants than in adults. The paediatric airway actively shapes how immune cells behave during the infection.”
The researchers then tested two antiviral drugs (remdesivir and RSV604). Both stopped the virus from multiplying, but only RSV604 also calmed the overactive immune response, reducing levels of a key inflammatory protein released by white blood cells – high levels of which are linked to more severe RSV disease in babies.
Remdesivir had no effect on this, suggesting that not all antivirals are equal when it comes to protecting the infant airway from immune-driven damage.
This suggests that treating severe RSV in babies may require more than just stopping the virus – it may also be important to calm an overactive immune response.
The researchers hope their findings and the new approach to research on RSV will accelerate the development of treatments better tailored to infants.
Dr Smith said: “Our model gives us a way to assess both sides of the problem at once. We can not only ask whether the drug stops the virus but also whether it helps control immune response in the infant airway.
“This work reinforces the idea that age matters in respiratory infection. Understanding how infant airways shape immune responses will be key to designing safer and more effective RSV treatments.”
Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash
By Elri Voigt
Being a researcher who studies tuberculosis in the lab is one thing, having the TB bug in your lungs is quite another. Spotlight sat down with two of a relatively small number of people who have experienced both.
One morning in April, Constance Schreuder, a senior medical technologist at a large research group at the University of Cape Town, was called into the campus’s occupational health office. “I was thinking, did I do something wrong?” she recalls.
When she got to the office, she says the doctor immediately opened the window behind him. She wondered “what is going on now?”.
The doctor told her that she has tested positive for the very illness she’s been studying at the South African Tuberculosis Vaccine Initiative (SATVI) for over two decades.
Part of Schreuder’s job involves working with post-mortem samples and tissues, as well as clinical trial samples sent from different TB research sites.
“We always protect ourselves by wearing the correct PPE [personal protective equipment]. So, we’re always safety first,” she says. “I was actually exposed [to TB] in the office where I sit. After all the years that I’ve been working in the lab.”
TB, caused by Mycobacterium tuberculosis, is typically spread when someone with the bacterium in their lungs coughs it up and those droplets are inhaled by others. The droplets are just the right size to hang suspended in the air, allowing TB to survive in a room for several hours.
Schreuder was confused by the diagnosis because she didn’t, and still does not, feel ill at all. She had been tested two months prior as a precaution after a PhD student in the lab had been diagnosed with TB and gotten very sick.
Her initial test results looked good. She had produced a sputum sample, a thick phlegm from the lungs, which was sent to the lab for molecular testing (using the GeneXpert platform). The test came back negative for TB DNA. She had also had a chest X-ray done, which showed no signs of TB in her lungs.
It was another test result that raised the alarm. In addition to the GeneXpert test, her sputum sample had been sent to be cultured. This involves putting the sample into a special tube, called a Mycobacteria Growth Indicator Tube (MGIT), and attempting to grow the bacteria if any is present. If TB bacteria has grown after around 50 days, then it means the TB bug was present in the sample. In Schreuder’s case, the TB bacteria did grow, although the bacterial count was low, a result in-keeping with her lack of symptoms.
Although she was sceptical of the result and wondered about a potential laboratory error, Schreuder’s thoughts immediately went to her close contacts – her 81-year-old mom who she sees on weekends, her pregnant daughter who lives nearby, and her son who lives with her. What did this mean for them, she wondered.
No one else from the office who had been tested showed any sign of TB disease, although Schreuder says that not everyone’s sputum sample had been cultured due to the cost of the test.
Only about one in ten people who are exposed to the bacterium will become sick with TB. In most people, the immune system contains and eventually starves the bacterium to death. In others, however, the bug survives inside the body and eventually causes illness, weeks, months, or even years later.
A silent form of TB
Schreuder very likely has what is called asymptomatic TB. This is a state where the bug is active in someone’s body, but it is not, or not yet, resulting in symptoms. There are many unknowns about this state, how much it actually contributes to TB transmission and how best to test for and treat it.
While there is much uncertainty about the prevalence of asymptomatic TB, some rough numbers exist. South Africa’s first National TB prevalence survey found that just over half of the participants with TB that was confirmed through molecular testing, did not report having any TB symptoms.
Schreuder says that she knew about TB symptoms but was under the impression that people had to show at least some symptoms if they were ill.
She says she was issued with a sick note, was told by the doctor at the occupational health office to go to a public healthcare sector clinic to get treatment, and that she was booked off for the next 14 days. People who are ill with TB generally become non-infectious after having taken TB treatment for around two weeks.
South Africa’s TB treatment guidelines does not recommend different treatment courses based on whether or not someone has symptoms. That means that Schreuder has to take the full six-month course of TB treatment.
‘I thought it was something very serious’
Schreuder’s experience is one side of the coin, the other side is a story from the same lab, one that may seem more familiar.
Tatenda Bvudzijena, an energetic young student, says he came to do his PhD at the SATVI lab because of the world class research that he felt he could learn a lot from. He shares an office space with several staff members at SATVI, including Schreuder. It was his TB diagnosis that had prompted the staff to get tested.
Bvudzijena describes himself as hard-working, so it was very unusual when he started feeling too tired to complete laboratory work near the end of 2025. He was finishing up the second year of his PhD at the time. He says he tried taking some vitamin B, but it didn’t help. Then he started to develop some of the typical symptoms of TB, persistent cough and weight-loss. The cough didn’t go away after he treated it with over-the-counter medicines.
“I had those coughing symptoms, then they disappear for a while, then it comes back again. It’s oscillating…coming back, stopping, coming back again,” he says.
Bvudzijena says a private sector doctor told him he might have asthma, but none of the medication he was prescribed – anti-inflammatories, cough syrup, antibiotics, and asthma pills – worked.
Meanwhile, he kept getting sicker.
“That’s when I was like, ‘no, this is not helping’. By that time, I had chest pains and I was losing a lot of weight,” Bvudzijena says. “I just remember back then I used to wear like a size 32 jeans…then I was wearing size 28…I was less than 55kg, but I used to be like 70kg,” he recalls.
He says he was starting to panic since the pain in his chest felt sharp. Gesturing to an area underneath his ribs on his left, he says: “I thought it was something very serious.” He adds: “At first I thought, maybe I could be having lung cancer, because I used to vape.”
Then, one Monday morning in February, Bvudzijena went to see another private sector doctor. This time he was immediately sent to get a TB test and a chest X-ray. “Your chest X-ray is showing symptoms suggestive of TB”, the doctor told him two days later.
Bvudzijena says he was both scared and relieved. He was relieved because TB can be cured and he did not have something incurable but also scared because seeing his own chest X-rays, he realised he was quite sick with TB.
Bvudzijena has to take the same six months course of treatment as Schreuder.
What taking TB treatment is like
In South Africa, “typical” or drug susceptible pulmonary (of the lungs) TB in adults is treated with a six-month treatment course – consisting of four drugs for two months and then two drugs for the next four months.
TB is mostly treated in the public healthcare sector, so even if someone has medical aid or access to private sector healthcare, they might still go to public sector facilities to get treatment.
TB treatment and diagnosis is covered under the minimum prescribed benefits for medical aid members. According to a notice by the Council for Medical Schemes, TB treatment can be made available to members of medical aid schemes through public sector clinics, but they should be given the option of getting their treatment through the private sector. Whether they can get treatment in the private sector is likely to depend on whether they can find a private sector doctor comfortable with treating TB and a pharmacy that stocks TB medicines.
Still showing no symptoms of TB when she started treatment, Schreuder says she was surprised to learn from the package insert that came with the medicine that the pills must be taken on an empty stomach. The initial two months is five tablets per day (dosage depends on a person’s weight), she explains grimacing.
She has had some side effects. At first, it was only constipation and her urine turning orange, a side effect of rifampicin, one of the four antibiotics used to treat drug-susceptible TB. But by the second month of taking the medication, she also started experiencing muscle and joint pains as well as burning feet.
Schreuder will start on the less intensive four remaining months of the course soon, when the regimen drops from four down to two antibiotics. But she worries about what the drugs might be doing to her body.
With TB already taking its toll on Bvudzijena, he says he started treatment knowing that he had to be serious about taking it as prescribed.
“I was in that situation whereby you know you’re very sick and based on the chest X-rays I was seeing, this [TB disease] was intensive. So like I had to take meds, I had to,” he says, tapping his finger on the table for emphasis.
He says he was surprised by the size of the tablets, eyes wide as he describes them. “They’re big! I’ve never seen something like that. It was my first time seeing a pill for TB,” he says.
For Bvudzijena, the side effects have been relatively mild, a runny stomach and a skin rash, as well as joint pain when he started the two-drug phase of treatment.
He says he started feeling better soon after starting treatment, got his appetite back, and his TB symptoms disappeared completely.
Two clinics, two different treatment experiences
But before they could start taking their treatment, Bvudzijena and Schreuder had to get access to the drugs, which was easier said than done.
Bvudzijena, upon getting his chest X-ray, says he was told nothing other than he needed to go to Groote Schuur Hospital. So he went, only to find that because Groote Schuur Hospital’s waiting rooms employ a triage system – where patients who are in the most critical condition are seen first – he’d likely have to wait several hours.
So, he left and later went to a doctor at another private hospital and got referred to see a specialist at that hospital. He says the specialist would have only been able to see him a week later. At his wits end, he went to campus health, who put him in touch with a nurse at a nearby public sector clinic.
Once at that clinic, he says he was well taken care of, got given a little green card, identifying him as a TB patient. This card is his ticket to travelling through the clinic quickly and not having “to wait in a long queue wearing a mask”.
“My only problem was from being diagnosed to getting help,” he says.
Schreuder, after being booked off, had Googled the nearest public sector clinic that offers TB treatment. The next day, on a rainy Friday, she drove from her home in Cape Town’s Northern Suburbs to a clinic in the Durbanville area. She wore a clean mask she had found in a bag, a remnant of the COVID-19 pandemic.
“I actually was there 06:30 in the morning because I wanted to just get it over with and start with this medication because they say if you drink it for 14 days, then you’re not infectious anymore,” she says.
At the clinic, she says she was taken to a separate room to wait by herself, as it turns out for five hours. Eventually she says she was helped by a nurse, who filled out her paperwork and took another sputum sample.
Another hour later, she says she left with six packs of TB medication, enough for the first month of treatment. But she had to stop at a private sector pharmacy on the way home because the clinic was out of vitamin B6, which she had been told to take to help with the potential side effect of “pins and needles in your hands and feet”.
Her frustrations with the system would mount. At a subsequent clinic visit Schreuder discovered that her phone number hadn’t been captured, meaning she hadn’t received the test results from her second sputum test. When she asked for her TB medicines to be dispensed to her ahead of time since she was already at the clinic, she says she was told the medicines were out of stock.
When she arrived for her next appointment at 12:00 on a Friday in May, she says the clinic seemed empty. When she eventually found a nurse, she claims the nurse told her she was only working until 12:00, and that the rest of the staff had left to attend a party for someone who had resigned, and that Schreuder must come back on Monday. A frustrated Schreuder says she didn’t accept this and eventually the nurse agreed to give her the medication.
“What’s worrying for me,” says Schreuder, “is, I said to her, ‘I work in this clinical trial lab where we want to find a cure for TB. But are we going to reach a TB free world if it [the health system] works like this?’.”
What needs to change?
Both Bvudzijena and Schreuder say it needs to be made easier for people with TB to start and collect TB treatment. They suggest that private sector pharmacies could be a convenient alternative to public sector clinics. Bvudzijena adds that stable patients could also collect their medication from selected community pharmacies or other collection points closer to home, reducing unnecessary travel and long waiting times.
He also touched on the need for better, clearer information for people who have just been diagnosed with TB about where they need to go, what documents they might need and how to start treatment.
“When you’ve just been told you have TB, you’re already worried,” he says. “The last thing you need is to be sent from one place to another without knowing where to get help.” He adds that there needs to be better coordination between private healthcare providers and public clinics.
Both touched on the stigma associated with a TB diagnosis. Schreuder says she received support from family members but otherwise it felt like people were simply checking that she had been cleared to go back to work. Bvudzijena says overall the reaction to his diagnosis was mixed. Some people like his roommates and friends were supportive, but not everyone was so understanding. “It was tough,” he says.
Change in perspective
Bvudzijena says that getting sick with TB changed his perspective on the research he’s involved with.
“What I realise now, after having TB, is that this research is about so much more than science. My work is focused on improving TB diagnosis so people can be diagnosed earlier, while many of my colleagues are working on better treatments and vaccines. After going through TB myself, I know how much that work can mean to someone who’s sick. It’s really going to change people’s lives,” he says.
To Schreuder, the experience has also been eye-opening but in a different way. She recounts some of the stories she heard while waiting at the clinic, a woman who has arrived at 05:30 but hours later still hadn’t been helped because her file was missing. A man who is afraid he’ll lose his job if he waits any longer. Patients sent to wait outside on cold benches and concrete floors, some looking very ill. Data from community-led monitoring group Ritshidze suggests that long waiting times is a common problem.
“I can fight my own battles, but what about all those that are too afraid to say something?” Schreuder asks.
Higher levels of circulating vitamin A are linked to better lung function in children and adults with asthma, while vitamin D shows similar benefits in adults, including slower biological ageing, finds the first study of its kind, published online in the respiratory journal Thorax.
Poor lung function is a key predictor of death, irrespective of whether or not a person has lung disease. And making sure that the lungs keep working well is essential for staving off long term respiratory conditions, explain the researchers.
Previously published research suggests that vitamins A and D both protect against and worsen asthma, as well as influencing lung development, depending on the dose and context, they add.
To clarify the role of these vitamins, the researchers drew on two groups of participants with asthma: 1165 children in the GACRS (Genetic Epidemiology of Asthma in Costa Rica Study); and 1041 adults in the ODOLLFA (Omic Determinants of Longitudinal Lung Function in Asthma).
Small molecules that fine-tune the activity of genes (serum microRNAs or miRNAs for short) and those that mark genes as either active or inactive (DNA methylation), plus levels of vitamins A and D, were measured in all the participants.
Lung capacity/health was assessed through measures of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the FEV:FVC ratio.
In adults, further analysis assessed whether methylation status and miRNAs influenced the association between the vitamins and lung function or epigenetic ageing – the response of genes to external biological and environmental factors which then promotes cellular ageing.
The findings showed that children and adults with asthma and higher vitamin A levels had better lung function (FEV1 and FVC) than those with lower levels.
And among adults with asthma, those with higher vitamin D levels of at least 30 ng/ml had better lung function than those with lower levels. They also had less evidence of epigenetic ageing, suggesting that vitamin D may help slow biological ageing, particularly in people with asthma, say the researchers.
“These findings emphasise the value of adequate vitamin D, not only for lung health but also in slowing age-related processes,” they write.
In people with asthma, vitamin D deficiency is more common and is associated with more severe disease, worse asthma control, higher inhaled steroid need and more frequent sudden worsening of asthma symptoms, they explain.
The researchers identified MiRNAs that regulate 248 genes commonly associated with vitamins A and D in both age groups, which, further analysis suggests, are involved in controlling inflammation and lung function.
This secondary analysis also revealed that changes in the expression of specific miRNAs strongly influence the effects of vitamins A and vitamin D on lung function and epigenetic ageing.
“To our knowledge, this is the first study to integrate vitamin A and D levels with lung function and epigenetic markers – miRNA expression and DNA methylation – in both children and adults with asthma,” write the researchers.
Lung function was inversely correlated with all age acceleration measures, reinforcing the link between respiratory health and ageing,” they add.
They conclude: “Our findings emphasise that epigenetic mechanisms play a key role in mediating the effects of vitamins on lung function in individuals with asthma, pointing to potential targets for personalised nutrition and therapeutic strategies in asthma care.”
In a linked editorial, Drs Sze Man Tse and Genevieve Mailhot of the CHU Sainte-Justine Research Center, Montreal, and the University of Montreal, caution: “While these findings open a novel line of investigation linking vitamin D, biological ageing and lung health, there is a need for further studies to clarify causality.”
But they add: “By examining the underlying biological mechanisms, [the researchers have] revealed a nuanced interplay between vitamins A and D, lung function, and their epigenetic mediators.
“Their findings highlight age-dependent and age-independent mechanisms, underscoring complex interactions between vitamin levels and lung physiology.”
And they conclude: “Overall, advancing our understanding of how nutritional exposures impact gene regulation may open new avenues for managing asthma across the lifespan.”
A South African clinical study that began in a research unit in Gqeberha (PE), Eastern Cape, has transformed global treatment of drug-resistant tuberculosis. Furthermore, the study’s findings were published this week in the New England Journal of Medicine (NEJM), the highest-ranked medical journal in the world.
The publication recognises that this research study has set the global standard for TB care.
The BEAT Tuberculosis clinical study, conducted at the Clinical Health Research Unit (CHRU) Isango Lethemba TB Research Unit in the Eastern Cape and King Dinizulu Hospital Complex in KwaZulu-Natal, enrolled more than 400 participants over two years during the Covid-19 pandemic.
The study was executed by the University of the Witwatersrand in collaboration with the National Department of Health and funded by the United States Agency for International Development (USAID).
“This project has gone full circle,” says Dr Francesca Conradie, principal investigator of BEAT Tuberculosis and a researcher at the Clinical Health Research Unit (CHRU), University of the Witwatersrand. “The results from this trial have changed international guidelines. Being published in the New England Journal of Medicine is proof that South Africa produces world-class research that improves the lives of patients globally.”
Treatment for the whole family
The primary aim of BEAT Tuberculosis was to evaluate the safety and effectiveness of a novel, shortened treatment regimen for DR-TB compared with the established standard of care. The standard treatment at the time required a seven-drug regimen administered over a minimum of nine months. BEAT Tuberculosis tested a streamlined regimen of four to five medications, including the newer agents bedaquiline and delamanid, administered over six months.
The BEAT Tuberculosis trial enrolled children, pregnant women and breastfeeding mothers alongside adults. These former groups are usually excluded from clinical research. The result is a treatment regimen that can be used across the entire family.
“This is a one-size-fits-all treatment regimen,” explains Conradie. “Adherence is much easier when the three-year-old, the teenager, the mother and the father are all receiving treatment of similar duration and composition. That simplicity saves lives.”
The study enrolled 10 pregnant women. All 10 women gave birth to healthy babies, and nine of them were successfully treated. BEAT Tuberculosis has since been cited internationally as a model for inclusive clinical research methodology, and the findings have influenced World Health Organization policy on the treatment of DR-TB globally, including for pregnant women and children.
South Africa’s National Clinical Advisory Committee already reviews and approves the regimen for pregnant women presenting with Drug-Resistant TB, while other provinces are adopting the treatment, particularly when treating children.
During 2024, South Africa had 249,000 people who were infected with active tuberculosis, and 54 000 died from the disease,” says Professor Norbert Ndjeka, Chief Director: TB Control and Management, National Department of Health. “Not only did BEAT TB produce world-class research, but it is also being implemented progressively across South Africa and globally and is internationally recognised. South Africa has accomplished something exceptional.”
Cambridge researchers have shown that severe pneumonia has three different subtypes, helping explain why some patients in intensive care units (ICUs) recover from their illness faster than others, while for other patients the disease can be life-threatening.
Their findings could in future help inform tailored treatments, allowing individual patients to receive the most appropriate therapies.
The current approach of classifying patients by their clinical syndromes without looking at the underlying biology risks missing what’s key
Andrew Conway Morris
Pneumonia is the commonest infectious cause of death worldwide, responsible for an estimated 2.5 million deaths per year. In severe cases, patients may need to be admitted to an ICU and given mechanical ventilation. Severe pneumonia accounts for six in 10 infections managed in intensive care, and spread of the infection within ICUs is a significant concern.
Doctors have long struggled to understand why patients whose condition looks similar clinically can have very different recoveries. Some respond quickly to treatment, while others remain critically ill for weeks or even die.
Dr Andrew Conway Morris from the Department of Medicine at the University of Cambridge and an ICU consultant at Addenbrooke’s Hospital, Cambridge, said: “Even though we’re able to treat the initial infection, many patients with severe pneumonia still struggle to come off the ventilator and can develop lung failure. Therapies to tackle inflammation in the lungs have had mixed results in clinical trials – some suggest they are beneficial, others that they’re harmful.
“The current approach of classifying patients by their clinical syndromes – sepsis, acute respiratory distress syndrome and so on – without looking at the underlying biology risks missing what’s key. Instead of asking ‘Does this patient have pneumonia?’, we should be asking ‘What’s the inflammatory pattern in this patient’s lungs?’”
In findings published today in Nature Communications, Professor Conway Morris and team recruited patients admitted with suspected severe pneumonia to the ICU at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust.
Severe pneumonia is usually diagnosed through a combination of symptoms, imaging and blood tests. Symptoms typically include fever or hypothermia, low oxygen levels, breathing difficulties and confusion.
Instead of relying only on blood tests or scans, however, the Cambridge team analysed immune cells, inflammatory signals, and gene activity in fluid taken from the lungs of the patients. They discovered that there are three distinct biological types – or ‘pneumotypes’ – of severe pneumonia, none of which could be reliably detected using standard blood tests, even though they were strongly linked to how patients recovered.
The most common pneumotype – accounting for almost half (49%) of cases – was characterised by immune suppression, significant damage to the lining of the lungs, and bleeding in the alveoli (tiny air sacs within the lungs). There were fewer signs of inflammation, which may explain why treatments targeting inflammation can fail or even harm some patients.
The second pneumotype – accounting for just under a quarter (23%) of cases – was characterised by a balanced immune response and active repair of damage to the lungs. Patients were most likely to recover faster from this pneumotype and require the shortest time on the ventilator, even though they initially looked just as ill as the others.
Patients with the most dangerous pneumotype – the one that most resembles ‘classic’ pneumonia – spent longest on mechanical ventilation and had prolonged critical illness. They had severe and persistent inflammation, with a flood of immature immune cells in the lung. This group may be most likely to respond to anti-inflammatory therapies, say the team.
Dr Mark Jeffrey from the Department of Medicine at the University of Cambridge, the study’s first author, said: “Even though on the surface, all of the patients seemed to have similar types of pneumonia, with comparable illness severity, oxygen levels and clinical diagnoses, their outcomes were very different.
“It was only when we drilled down and looked at patterns of inflammation that the differences became apparent. Severe pneumonia is not a single disease, but several biologically distinct conditions that happen to look alike. This helps explain why ‘one-size-fits-all’ treatments – including some immune-modulating drugs – have often failed in clinical trials.”
The tests used to determine the pneumotypes are too complex to enable rapid classification, but the researchers hope to develop a simplified tool that could help them stratify the patients and ultimately offer tailored treatments.
Dr Vilas Navapurkar from the John Farman Intensive Care Unit at Addenbrooke’s Hospital said: “If we know which subtype of pneumonia an individual has, we can potentially tailor their treatment more precisely, boosting the immune response in some, while calming harmful inflammation in others. This has the potential to help critically ill patients, reduce deaths from pneumonia, shorten ICU stays and cut unnecessary antibiotic use.”
The study was funded by Addenbrooke’s Charitable Trust, the National Institute for Health and Care Research Cambridge Biomedical Research Centre, and The Forster Foundation. Professor Conway Morris is a Fellow at Emmanuel College, Cambridge.
A new study published in the journal Neuron shows for the first time that targeted control of human breathing rhythm can influence decision behaviour by modulating heart and brain function. The research team was able to demonstrate that prolonged exhalation increases heartrate variability and the brain’s reward sensitivity, thus enabling us to make bolder decisions.
Accelerated breathing and rapid heart rate often lead to quick decision–making. Judgements under these circumstances, can lead to a more cautious decisions to minimise potential loss – whether it is making investments under time pressure, during a critical employee meeting, or when quickly selecting a meal. In contrast, slow breathing and a calmer heart could presumably lead to assessing the situation more positively and making bolder decisions.
New Perspective: Body, Brain, and Decision in Harmony
Traditional theories assume that decisions arise in the brain. The present study investigated how the interplay of different organs can influence brain function and thereby control our decisions. It was spearheaded by Prof Soyoung Q Park in cooperation with institutions such as Neuroscience Research Center at Charité – Universitätsmedizin Berlin, Freie Universität Berlin, and German Naval Institute of Maritime Medicine.
“Our decisions are rarely determined solely by external information. Rather, our judgment emerges from the interplay between cognitive processes and our current bodily state. It was previously unknown how the conscious regulation of our body, for example through targeted breathing, could actively control our decision–making process. We wanted to create a physiological shift using slow breathing pattern to change the quality of our decisions,” explains Soyoung Q Park, head of the Department of Decision Neuroscience and Nutrition at DIfE, summarising the research question.
In the study, 41 healthy participants were observed in a state-of-the-art multi-methods research setting as they made risky decisions while adhering to specified breathing protocols. The participants followed visual breathing cues and breathed either in their individual natural rhythm or slower with an extended exhalation (2:8 inhale-exhale ratio). While they breathed, they were asked to make several risk decisions. Meanwhile, the researchers captured brain function using functional magnetic resonance imaging and simultaneously monitored breathing parameters, heart activity, skin conductance, and pupillary reactions. By combining these measurements, the researchers were able to investigate whether extended exhalation not only lowers heart rate but also leads causally to modulated reward processing in the brain.
The Body’s State Influences Our Decisions
The scientists found that extended exhalation led to riskier decisions by slowing down heart rate. Notably, the risky decisions were more guided by potential rewards, while the consideration of potential losses remained unchanged. Furthermore, there was increased activity in the ventromedial prefrontal cortex and the precuneus area. These two key brain regions influence both the time intervals between heartbeats – known as heart rate variability – and reward sensitivity. “Our study thus underscores the transformative role of breath–based interventions. The interplay between breathing and cardiac dynamics makes the brain more receptive to rewards,” explains lead author Wenhao Huang, interpreting the results.
The Practical Benefits of Breathing Techniques
The findings expand the field of body-brain interaction research and support so-called neurovisceral models, which posit that physical condition strongly influences cognitive processes. Park explains: “Breathing techniques have accompanied humanity for millennia across various religions and cultures. With this study, we provide scientific proof that it is a reliable and targeted method capable of controlling our decisions.”
Thus, breathing techniques represent a simple, inexpensive, and easy-to-learn option for everyday self-regulation. Moreover, they have immense potential value in clinical settings as an adjunctive, non-pharmacological strategy – for example, for conditions such as anxiety disorders or depression, which are characterised by autonomic dysregulation and altered reward perception.
The next step should be to investigate whether the observed effects can be generalised to a broader clinical population, such as people with overweight. “Since dietary decisions are strongly influenced by reward assessment and physical state, targeted breath regulation could also play a role in consciously perceiving and more effectively managing eating behavior,” Park summarises for future research activities.
