Severe pneumococcal disease requiring hospitalisation, most commonly pneumonia, can be a sign of previously undiagnosed blood cancer and immunodeficiency in adult patients, according to a study from the University of Gothenburg.
The study followed 156 individuals who developed invasive pneumococcal disease and required hospital care in the Region Västra Götaland between 2018 and 2023. The median age of the patients was 70 years.
The researchers examined the patients’ immune system by measuring antibody levels and studied the presence of M protein, known as a risk marker for blood cancer. The control group consisted of 64 individuals matched for age and sex who did not have invasive pneumococcal disease.
In the pneumococcal disease group, one in four individuals had M protein in their blood, a marker that may be present in blood cancer or in precursor conditions. The examinations led to seven patients being diagnosed with blood cancer, while another twelve were diagnosed with a condition that can, in some cases, progress to blood cancer.
Routine screening should be considered
Eight patients were found to have immunodeficiency, seven of whom were able to start preventive treatment against new, severe infections. These findings were considerably less common in the control group.
The results, published in the journal Scientific Reports, suggest that screening for M proteins and antibody levels in adults with invasive pneumococcal disease should be considered, according to the researchers, as the disease can reveal previously undiagnosed blood cancer and immunodeficiency.
“Currently, these tests are not routinely performed after a severe pneumococcal infection. As a result, we may miss patients with undiagnosed blood cancer or immunodeficiency and therefore missing the opportunity to initiate treatment,” says Tor Härnqvist, a doctoral student at the University of Gothenburg, an infectious disease physician at NU Hospital Group, and one of the lead authors.
Importance of tailoring vaccinations
Karin Bergman is a doctoral student in the same research group and an infectious disease physician at Södra Älvsborg Hospital. The study is part of her doctoral thesis, which she will soon defend at the University of Gothenburg, in which she also demonstrates how the pneumococcal bacteria causing severe disease have changed since the pneumococcal vaccine was introduced into the Swedish childhood vaccination programme.
The bacterial serotypes covered by the childhood vaccine have decreased sharply but have largely been replaced by other serotypes against which the vaccine offers no protection. Older adults and individuals with underlying conditions, particularly cancer and compromised immune systems, are frequently affected by these serotypes.
“The results show that recommendations on pneumococcal vaccines for adults need to take into account which vaccines are used in children and which bacterial serotypes subsequently circulate in the community,” says Karin Bergman.
3D reconstruction of rhinovirus-infected human airway epithelial cells. Virus-infected cells (multicoloured) can be seen protruding from the epithelial layer during cell extrusion. Credit: Faith Fore. An AI-assisted editing tool was used to sharpen this image.
The epithelium, a layer of cells that forms a protective barrier between the body and the outside world, was the first organised tissue to evolve. Epithelial cells lining our airways are mainly seen as a structural barrier, but cell biologist Jody Rosenblatt, who runs a lab at the Crick and King’s College London, believes their evolutionary history suggests they’re playing a much more active role in infections.
“The airway lining is the body’s first physical barrier against inhaled threats like viruses,” says Jody. “It would make sense for it to take direct action.”
To investigate this, Jody’s team studied rhinoviruses, which are the leading cause of the common cold. They usually cause mild illness, but they can cause more serious respiratory disease in young children, older people, people with weakened immune systems and those with chronic lung conditions such as asthma or COPD.
Their new study, published today in Science Advances, shows that airway cells respond to rhinovirus infection by physically pushing infected cells out of the tissue, in a process the researchers have named ‘virus-induced cell extrusion’ or ‘VICE’.
As first author and Postdoctoral Research Fellow Faith Fore explains, “We studied rhinovirus infection in human epithelial cells grown in the lab, and we observed that when the cells were able to work together as a healthy layer, they could remove infected cells and limit infection within the tissue.
“But when we experimentally disrupted the barrier by breaking down junctions between epithelial cells, more virus particles built up in the epithelial layer. We also observed virus-induced cell extrusion in mouse lung tissue, supporting the relevance of the mechanism in a more complex tissue environment.”
The researchers also observed that VICE happens in two distinct waves. The first begins rapidly, before the virus has fully entered the cell, involving the cell’s ability to sense mechanical changes, while a second wave occurs later, triggered by the virus replicating inside the cell, leading to cell death. “These two waves allow the epithelial cells to kick into action straight away, without the need for signals from immune cells that have recognised the virus,” says Jody.
A ‘double-edged defence’
This early defence mechanism helps remove most infected cells from the airway lining within 24 hours, maintaining the integrity of the barrier. But, there’s a downside. “The expelled cells remain alive and infectious, potentially allowing the virus to reach new cells,” explains Faith. The team confirmed this by adding extruded airway cells to healthy cells in a dish, which subsequently were infected with the virus after just six hours.
Faith continues, “The airway gets rid of the infected cell, but it doesn’t destroy the virus. Because the expelled cells can still infect new cells, it creates a double-edged defence. Extrusion helps the tissue clear the immediate infection, but the expelled cells remain a potential source of viral spread.”
An overlooked mechanism
Jody believes that this mechanism should be taken into account when assessing responses to infections. It may have been overlooked because some commonly used laboratory models do not recreate the cell-to-cell junctions that the team has now shown are required for VICE to occur.
“Understanding these fundamental tissue defence mechanisms could change how we think about the earliest stages of viral infection.”
“Our study suggests that cells lining our tissues possess evolutionarily ancient mechanisms for protecting themselves,” she says. “Understanding these fundamental tissue defence mechanisms could change how we think about the earliest stages of viral infection.”
Faith agrees, “We typically think of the cells lining our airways as a simple physical barrier, leaving the heavy lifting of clearing infections to the immune system. What we found is that the epithelium itself actively fights back by physically throwing out infected cells.”
The researchers are now planning to investigate how widespread this defence mechanism is across respiratory viruses, what determines whether extrusion protects the airway or promotes viral spread, and how viruses might evade or exploit the response.
Many people who report with TB symptoms at South Africa’s public sector clinics do not receive TB tests. Testing more of these people is one of the most effective things we can do to reduce rates of TB disease and death, according to a major new modelling study.
While South Africa has made substantial progress against tuberculosis (TB), we are not on track to meet key targets set for 2030. This is according to a new modelling paper published in the journal Global Health Action.
TB incidence in South Africa was projected to decline by 46% by 2030, relative to a 2015 baseline. The World Health Organization (WHO) End TB target adopted by South Africa aimed at an 80% reduction in incidence. TB mortality was projected to decline by 54%, against the End TB target of 90%.
The researchers also published uncertainty intervals around these estimates. Even though these intervals are relatively wide, their upper limits are below the End TB targets, suggesting that it is unlikely that South Africa will reach the targets by 2030. The modelling however also identified interventions that could help South Africa get closer to the targets.
The new research is an extension of Thembisa, an existing mathematical model of HIV and TB in South Africa. University of Cape Town epidemiologist Dr Leigh Johnson, who is the lead author of the new study, is also the key driving force behind Thembisa.
Identifying what works
The researchers estimated which of a long list of interventions would have the greatest impact against TB. In technical terms, they looked at how varying 27 different parameters linked to TB interventions impacted projected TB incidence and mortality from 2025 to 2040 by calculating correlation coefficients (see the paper for a more nuanced explanation).
They found that the greatest reductions in TB would be achieved if a high percentage (89%) of people reporting with TB symptoms were tested using new point-of-care TB tests. This would result in a 49% reduction in average TB incidence and a 67% reduction in average TB mortality, relative to a scenario in which there are no changes to current programmes. TB symptoms include persistent cough, chest pain, night sweats, fever, and unexplained weight loss. There is good evidence that many people who report with these symptoms at clinics are not offered molecular TB tests.
The World Health Organization earlier this year recommended the use of such new point-of-care TB tests. These tests aren’t yet in general use in South Africa, although they are being evaluated in pilot projects. The new tests can be run on both sputum and tongue swabs. For now, most molecular TB tests in South Africa still involve someone producing a sputum sample – which some people struggle with – and the sample being transported to a lab for testing.
The researchers also found that high rates of door-to-door testing with the new point-of-care tests could reduce TB incidence and mortality by 38% and 49% respectively, while combining high rates of door-to-door testing and digital chest X-ray screening in asymptomatic individuals could reduce TB incidence and mortality by 17% and 21%.
Even without the new tests, there are substantial gains to be had if testing was stepped up in people with symptoms. TB incidence could be reduced by as much as 29% if the level of sputum testing in individuals seeking care for TB symptoms were increased to the upper bound considered by the researchers.
Once people have been diagnosed with TB and start taking TB treatment, they typically become non-infectious within around two weeks. Diagnosing people more quickly thus results in people remaining infectious for shorter periods, thus slowing TB transmission.
Other influential parameters identified by the researchers include the extent to which COVID-19-related behaviour changes are sustained, the rate at which people living with HIV start taking antiretroviral treatment (untreated HIV is a major driver of TB), and the combined uptake and efficacy of 3HP, a relatively new form of TB preventive therapy.
Testing is the key
“We found that the rate of testing in people seeking treatment for TB symptoms is the most important driver of future TB incidence and mortality,” wrote the authors.“This finding is not surprising given the historically low rates of TB testing. In studies of patients seeking treatment for TB symptoms in South African health facilities, the proportion who received a TB test has been highly variable, ranging from 3% to 84%, with a median of only 30%. Similarly low rates have been reported in other countries with high TB burdens.”
The study authors write that these low rates of testing reflect the non-specificity of TB symptoms and healthcare workers’ concerns about the cost and time required to collect sputum specimens and to send them to a central laboratory for molecular testing. In one South African study, they point out that 36% of all people attending clinics had symptoms suggestive of TB.
“Conducting TB testing in such a large fraction of primary care attendees may be infeasible,” they write.
“Achieving high levels of testing in people with TB symptoms could require levels of laboratory testing beyond current testing capacity. However, new point-of-care tests performed on tongue swabs or sputum present an important opportunity to increase levels of TB testing in symptomatic individuals at reduced cost, without placing additional strain on laboratories.”
In addition to reduced cost, the new point-of-care tests also offer quicker results and have lower operational requirements. The main potential benefit of these tests over existing lab tests is thus that they are likely to be used much more frequently.
Regardless of the testing platform, the study authors argue there is a need to strengthen adherence to existing guidelines for systematic testing of all patients with symptoms suggestive of TB and that we need a larger healthcare workforce dedicated to TB diagnosis, better supply chains, and better monitoring systems to identify where and why symptomatic patients are not being tested.
Disclosure: The study reported on here was supported by the Gates Foundation. Spotlight receives funding from the Gates Foundation, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
Initial chest radiograph in a 47-year-old man with silicosis showing subtle opacities in the right lower zone. CMAJ, 2026.
A case study in the Canadian Medical Association Journal describes a 47-year-old man who visited an emergency department for a minor injury to his lung and was found to have lung nodules after a computed tomography (CT) scan. He was diagnosed with silicosis. He had worked with engineered stone for the past 10 years for a company that made countertops and, after diagnosis, he was advised to stop exposure.
During the next 18 months, after referral to an occupational lung disease clinic, the patient’s lung condition worsened. He is currently awaiting assessment for a lung transplant.
“This case example supports calls for regulatory reform, mandatory surveillance, and proactive worker education in industries using engineered stone,” writes Dr Susan Tarlo, respiratory physician at University Health Network (UHN) and professor of medicine, Department of Medicine and Dalla Lana School of Public Health at the University of Toronto, Toronto, Ontario, with coauthors. “It underscores the health risks from the absence of adequate occupational health monitoring.”
Linking cases of silicosis to working with engineered stone has been fairly recent, with the earliest cases reported in the early 2010s in Spain and Italy then other parts of the world.
People who work in small businesses that may use dry cutting and processing techniques may be more vulnerable than those working at larger companies who mandate wet cutting and safety protocols. A large proportion of people affected are immigrants or members of racialised or marginalised communities who may face language barriers, lack insurance, or lack access to occupational health supports.
Australia has banned the use of engineered stone because of the health hazards associated with manufacturing.
The authors urge awareness for workers and health care practitioners.
“Health care providers should consider this diagnosis in patients working with engineered stone, and in countertop manufacturing and fitting, since early identification and removal from further exposure can greatly improve the prognosis.”
“In the absence of a ban on the use of engineered stone, increased knowledge among workers and health care practitioners is essential for implementing preventive measures, raising clinical awareness, informing policy decisions, and guiding future public health interventions,” the authors conclude.
Cystic fibrosis promotes chronic bacterial infections by impairing the protective barrier of the airways. Scientists at the University of Geneva (UNIGE) have discovered that this dysfunction is caused by the abnormal activation of a protein, connexin 43, which disrupts cellular organisation and compromises the integrity of the airways.
The team has not only shed light on this molecular mechanism using 3D models of cells derived from human lungs, but has also succeeded in correcting the defect using molecules already undergoing clinical trials in dermatology and oncology. Preventing pathogenic bacteria from attaching to the airways of people with cystic fibrosis could therefore help limit serious complications. These findings are published in the journal Communications Biology.
Despite significant therapeutic advances, chronic pulmonary infections persist in many patients with cystic fibrosis. Eradicating respiratory pathogens therefore remains a major challenge. In previous work, the team of UNIGE professor Marc Chanson, discovered that this vulnerability to infection stemmed from abnormal adhesion sites on the surface of respiratory cells – true “anchor points” to which bacteria attach firmly. “But to develop treatments, we first needed to understand the underlying mechanisms,” explains Marc Chanson.
A protein at the origin of bacterial anchor points
Connexin 43 is a protein known for its role in communication between cells, a process essential to the functioning of tissues and organs. In the airways, it is normally active only when cells need to regenerate. In people with cystic fibrosis, however, it remains abnormally active, triggering a cascade of dysfunctions.
“Using 3D models of cells derived from human lungs, we discovered that prolonged connexin 43 activity alters cell communication, disrupts cell orientation, and progressively disorganises tissue integrity,” says Mehdi Badaoui, senior lecturer in the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine and first author of the study. “It then promotes the formation of the anchor points to which the bacteria responsible for respiratory infections attach.”
Restoring the integrity of the airways
By blocking connexin 43 activity in their 3D models, the research team was able to restore cell orientation, re-establish the spatial organisation of cells, and prevent the formation of anchor points. “Mimetic peptides – short synthetic molecules already used to promote wound healing – drastically reduced the ability of bacteria to colonise respiratory cells,” explains Mehdi Badaoui.
“These findings demonstrate that the regulation of cell communication by connexin 43 is a fundamental element in maintaining pulmonary defence,” concludes Marc Chanson. “By targeting the deep mechanisms underlying airway dysfunction, our results could offer an additional treatment approach.”
For generations, a stethoscope has been one of the most essential tools for diagnosing pneumonia. But a new study suggests that what doctors hear through it may depend on who is listening.
In this cohort study, US investigators who are part of the Pediatric Emergency Care Applied Research Network analysed data from children and teens diagnosed as having community-acquired pneumonia (CAP). The findings showed that clinicians often disagreed about their findings on physical exam, including decreased breath sounds, crackles (wet, bubble-likes sounds when air flow is blocked), and rhonchi (abnormal breathing that sounds like snoring or rattling) – symptoms frequently associated with pneumonia.
Current US guidelines recommend diagnosing CAP based on clinical findings rather than chest X-rays in children who are treated as outpatients.
Same patient, different findings
For the study, published in JAMA Network Open, researchers analysed data from 252 participants, ages 3 months to 17 years, diagnosed with CAP at one of seven academic paediatric emergency departments across the United States. Two clinicians independently examined each patient within 60 minutes of one another and recorded their findings.
None of the physical exam findings met the researchers’ predetermined threshold for acceptable interrater reliability, a measure of how much different clinicians agree when analysing the same data or event. Wheezing (kappa value [κ], 0.50) and chest retractions (κ, 0.49) were the exam findings clinicians agreed on the most. Even so, agreement was modest.
Agreement was significantly lower for decreased breath sounds and crackles, which both had κ values under 0.25.
The findings raise questions about how heavily clinicians should rely on listening to the lungs when diagnosing pneumonia.
“This variability is not a trivial concern,” write Susan Lipsett, MD, of Boston Children’s Hospital, and Mark Neuman, MD, MPH, of Harvard Medical School, in an accompanying commentary. When examination findings vary depending on the observer, “their utility as diagnostic anchors is diminished” and their ability to appropriately guide treatment is compromised.
“If physicians cannot consistently agree on the presence of auscultatory findings, treatment decisions may hinge more on examiner interpretation than underlying pathology,” Lipsett and Neuman write. “This variability may contribute to well-documented differences in antibiotic prescribing and chest radiograph use across institutions.”
Why lung sounds can be hard to interpret
Several factors could explain the disagreement. Accurately interpreting lung sounds can depend on background noise, patient cooperation, and clinician experience—factors that “become even more challenging in a busy emergency department,” write Lipsett and Neuman. Children also have more flexible chest walls, which may make it harder to determine exactly where the sounds originate. What’s more, clinicians may also use terms like “crackles” to refer to slightly different things.
The commentators argue that the results strengthen the case for objective risk-assessment tools that combine factors such as fever, oxygen saturation, demographics, and selected clinical findings rather than relying on individual lung sounds.
“By quantifying risk and reducing dependence on subjective auscultatory interpretation, clinical prediction tools may mitigate interobserver variability and promote more consistent decision-making regarding imaging and antibiotic therapy,
Russell Rensburg is the Divisional Director of the Rural Health Advocacy Project which hosts the TB Accountability Consortium. (Photo: Supplied)
In March 2024, a pivotal clinical trial was launched to evaluate what might well become the first new tuberculosis vaccine on the market in more than a century. As anticipation mounts for the trial to deliver results, Russell Rensburg argues that we need to start preparing for a rollout of the jab, but that we should think of preparation more widely than just the technicalities of regulatory approval and drug supply.
Over the past few weeks, there have been ongoing discussions about a potential new TB vaccine coming to South Africa.
The leading new vaccine candidate M72/AS01E TB or M72 for short is currently being evaluated in a large phase three clinical trial that started in March 2024. The trial has been running ahead of schedule and it is possible that results might be ready in the next year. If those results are positive, registration with the South African Health Products Regulatory Authority should follow quite soon after.
As all this happens, preparations for possible future manufacturing of the jab are already underway. In July, the Serum Institute of India announced an agreement with the Gates Medical Research Institute to prepare for large-scale production should the trial be successful and the vaccine approved.
And at the same time South Africa’s National Department of Health has started to engage in discussions about the roadmap for a possible vaccine rollout.
The optimism is high, and rightly so. It’s the first time in more than 100 years that we have reached this point with a new TB vaccine. Given the size of South Africa’s population at approximately 63 million people, its share of TB deaths worldwide is striking. WHO data shows that of the over 1.2 million TB deaths, around 54 000 were reported in South Africa. The idea that a new jab can arrest the alarming death rate of this curable disease and change the trajectory of TB in the country is exciting.
But the point that we are at should also prompt an urgent question. If a new TB vaccine proves successful, will South Africa actually be ready to use it?
For a country carrying one of the world’s highest TB burdens, a successful vaccine could fundamentally change our response to the disease. But the regulatory approvals that we will hopefully see next year or the year after would only be the beginning.
Getting community buy-in
To effectively roll out this vaccine, South Africa would need the buy-in of communities who trust that this vaccine could help them and are willing to encourage their fellow community members to take it up.
This negotiation could be harder than we think.
The country does not have to wait for the vaccine to be approved to begin this work. The opportunity to start building the community trust already exists. How? With the current rollout of a new TB test.
The National Department of Health is implementing a demonstration project to assess the health system’s readiness to introduce a new near point-of-care TB diagnostic test into the public healthcare system. The test would mean that people can get TB tests done at the clinic and get a result virtually immediately.
Many of South Africa’s TB deaths are due to late diagnosis. The new test presents the opportunity to shorten the gap between testing and diagnosis (samples don’t have to be sent off to labs) and could result in earlier initiation into care, which will potentially contribute to reduced mortality.
The near point-of-care testing sites are being deployed across the country in district hospitals, community health centres and primary healthcare clinics.
But a very important part of that work is not simply understanding whether the health system is ready for this diagnostic approach, it’s how communities are engaged and mobilised to understand and use it.
Testing community engagement
The community mobilisation and demand-creation component allows us to work directly with communities to understand what it takes to introduce a new TB intervention in a way that does not simply place a new technology into the health system and assume that people will use it.
Alongside measuring diagnostic performance, we should be deliberately testing models of community engagement: working with community health workers, TB survivors, civil society organisations and trusted local leaders; building people’s understanding of TB; listening to their concerns; identifying misinformation early; and understanding which messages, platforms and messengers people trust.
If we do this well, when a TB vaccine eventually becomes available, we will not be starting the conversation from zero. We will already have communities that have been part of the journey of TB innovation, systems for listening and responding to their concerns, and trusted people who can help communities navigate new information. That is what genuine vaccine preparedness should look like. It is not only preparing the regulatory pathway, procurement systems and cold chain. It is preparing the people and communities for whom the vaccine is ultimately intended.
Yet community engagement is too often treated as something that happens at the end of the process: develop the intervention, approve it, procure it and then ask civil society to persuade people to use it.
Trust cannot be manufactured through a communications campaign launched three months before rollout. Trust in a vaccine is inseparable from trust in the health system delivering it. That is why community investment should be considered part of vaccine preparedness itself—not an optional communications budget added later.
The civil society bridge
Civil society has a particularly important role here. Government develops policy, researchers generate evidence and health workers deliver services. Civil society often provides the bridge between those systems and communities.
Community organisations understand local languages, stigma, misinformation, barriers to accessing care and, importantly, the questions people may be reluctant to ask government or healthcare providers.
We should therefore begin strengthening community systems now: building the capacity of trusted community leaders; developing TB vaccine literacy; establishing mechanisms for community-led monitoring; and integrating conversations about vaccination into existing TB, HIV and primary healthcare services.
This is not about convincing people to take a vaccine that has not yet been approved. It is about creating the conditions in which people can eventually make informed decisions.
Ultimately, the measure of success will not be how quickly South Africa approves or procures a new TB vaccine. It will be whether the people who stand to benefit from it understand it, trust the systems delivering it, and are able and willing to access it.
The scientific breakthrough may happen in a laboratory. But whether it changes the trajectory of TB in South Africa will be decided in our communities.
– Rensburg is divisional director of the Rural Health Advocacy Project, which hosts the TB Accountability Consortium.
Disclosure:Thispiecewas published by Spotlight – health journalism in the public interest. The Gates Medical Research Institute mentioned in this article is a non-profit organisation and subsidiary of the Gates Foundation. Spotlight receives funding from the Gates Foundation but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
Researchers explore how a key factor can mitigate or promote tuberculosis transmission.
Tuberculosis bacteria. Credit: CDC
Tuberculosis (TB) is a leading cause of infectious disease deaths, claiming over 1 million lives every year. It spreads through the air when an infected person coughs, sneezes, or exhales, and drug-resistant strains and asymptomatic spreading are growing concerns. Curbing TB transmission is an urgent public health challenge, yet scientists still don’t understand how airflow and other environmental factors influence that spread.
One problem is that studies of infectious disease transmission have focused mainly on population-level assessments or individual immune responses. But understanding how airflow and mixing influence transmission in indoor spaces requires expertise in fluid physics and computational modelling.
An interdisciplinary team including researchers at MIT and the University of Texas Southwestern Medical Center has now combined animal transmission experiments with quantitative particle tracking and flow modelling to understand how some lab-based environments can promote the spread of respiratory infectious diseases such as TB, while others mitigate that spread.
A key factor in predicting infectious transmission was not just the total ventilation rate but, more importantly, the local pattern of airflow driven by the design – such as air leakage, inflow and outflow locations, and forces created by an infected individual.
“The local airflow patterns turn out to be pivotal,” says Lydia Bourouiba, the Japan Steel Industry Chair Professor at MIT and faculty lead of the Fluid Dynamics of Disease Transmission Laboratory, part of the Fluids and Health Network within the Institute for Medical Engineering and Science (IMES). “Our team’s findings provide some of the clearest evidence I’m aware of showing the importance of accounting for [airflow] inhomogeneity and its effects when designing for airflow detailed patterns. This insight is critical when building or retrofitting an indoor space to mitigate airborne transmission, or when designing an airborne transmission study.”
The research is an important step toward connecting laboratory infectious disease studies with how people spread such diseases in the real world. The team hopes their insights can extend beyond their model system and show the importance of flow physics in building designs to prevent the spread of airborne diseases indoors.
“Despite recent pandemics and epidemics, there is still resistance to incorporating airflow in routine infectious disease prevention tools,” Bourouiba says. “Infrastructure could be retrofitted at relatively low cost, but the paucity and difficulty of gathering direct evidence prevents broader adoption of flow physics as a tool for indoor health. This study helps provide such evidence.”
Joining Bourouiba on a paper about the work are Yash Kulkarni, a postdoc at IMES, who led the fluid and aerosol physics components; Kubra Naqvi, lead author and a postdoc at UT Southwestern; Michael Shiloh, a professor at UT Southwestern, who led the multiyear effort to reestablish a classic tuberculosis transmission model; Hui Ouyang, an assistant professor of aerosol engineering at UT Dallas; Yuhui Guo, Deepak Sapkota, and Arabella Martin, all UT Southwestern PhD students; Pei Lu and Victoria Ektnitphong, research associates at UT Southwestern; Shibo Wang, a University of Minnesota researcher; Beatriz Dias, a UT Southwestern instructor; Bret Evers, an associate professor at UT Southwestern; and Lenette Lu, assistant professor at UT Southwestern.
Opening the black box
When people exhale, talk, cough, or sneeze, tiny microdroplets and bioaerosols launch from their mouths, carried forward by a cloud. If infected by a respiratory disease, these bioaerosols can contain pathogens that can infect others. Disease transmission depends on pathogen survival in the air, which is influenced by temperature, humidity, and ventilation.
In 1882, German physician and microbiologist Robert Koch first established an animal model for the study of tuberculosis pathogenesis. Decades later, researchers demonstrated airborne transmission of tuberculosis between people and animals.
These early experiments have proven difficult to replicate in today’s modern, biosafety-grade facilities. This new study reveals the difficulty comes from stringent containment and ventilation requirements, which can dramatically influence airflow in experiments.
“Host-to-host transmission is an obligatory evolutionary phase of respiratory pathogens, yet it has been considered too intractable or complex to be amenable to systematic investigation, hence is commonly relegated to a black box. Our work opens that black box,” says Bourouiba, who is professor in MIT’s departments of Mechanical and Civil and Environmental Engineering, and an IMES core faculty member.
To quantify how local airflow patterns impact infectious disease transmission, the researchers redesigned and modelled the early studies for modern high-containment lab facilities — including their seal, inflow, outflow, and exhaust pathways — and quantified particle and bacteria-laden particle release and dispersal. They released tracer particles and bacteria into a compartment and modelled recovery from air sampled on the other side under differing airflow rates, designs, and leak configurations.
The MIT team carried out computations, benchmarked against particle release experiments. The results revealed how important seemingly small details such as leakage paths could be.
“Even a small leak could short-circuit the airflow by drawing fresh air directly toward the exhaust, rather than drawing contaminated air across the containment chambers,” says Kulkarni.
Advancing TB research
To date, uneven indoor airflow patterns have not been fully harnessed as part of a risk mitigation strategy.
“By systematically defining how airflow and design influence biological exposure, we were ultimately able to restore transmission and create a system that can now be used to ask fundamental questions about the bacterial, host, and environmental factors that determine tuberculosis spread,” says Naqvi.
“I began working to reestablish this seminal TB animal transmission model nearly 10 years ago, and it proved far more challenging than I anticipated,” says Shiloh. “I hope this work serves as a reminder that meaningful scientific advances often require patience and perseverance.”
“This work illustrates how crucial it is to support synergistic collaborations integrating complementary disciplines to tackle research bottlenecks – and to standardise reporting norms across laboratories,” Bourouiba says. “If different labs have varying airflow patterns from uncontrolled leaks or seal details, that physical variability can overwhelm the biological signals researchers seek. Beyond its foundational impact for TB transmission studies, our work shows that opening the black box of transmission provides mechanistic insights: Detailed airflow pattern control can enhance or mitigate airborne transmission – making it exploitable as a prevention measure in crowded gathering spaces.”
This work was supported, in part, by the National Institutes of Health, the National Science Foundation, the Burroughs Wellcome Fund, MathWorks, and the Translational Research Institute for Space Health.
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.
