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Triple-dose Regimen May Permanently Clear HIV in Infected Newborns

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OHSU-led discovery in animal model could advance quickly to clinical trials in people

Research from the lab of Jonah Sacha, PhD, at OHSU, has identified a one-time regimen of therapies for newborns with HIV that, if given within three days of birth, could permanently clear the virus. The research team hopes to use the animal model results to move into a human clinical trials. (OHSU/Christine Torres Hicks)

Every year, more than 120 000 newborns worldwide contract HIV, a global health burden that requires lifelong treatment for millions of people – assuming they have access and can afford it. New research led by Oregon Health & Science University suggests another possibility: a one-time regimen of therapies given to newborns within three days of birth to permanently clear the virus. The research was published in the journal Nature Microbiology.

“The really exciting part is that it could go to clinical trials immediately to eliminate HIV infection in newborns,” said co-lead author Jonah Sacha, PhD, professor and chief of pathobiology and immunology at OHSU’s Oregon National Primate Research Center and Vaccine and Gene Therapy Institute. “The next step after that is to test if this can work in newly exposed adults.”

The research involved many collaborators and nonhuman primates at both the Oregon and California national primate research centres.

Researchers tested three distinct treatments that were delivered for a few weeks: neutralising antibodies, standard antiretroviral therapy, and an experimental monoclonal antibody known as leronlimab.

Each of the individual treatments has been tried previously and failed to permanently clear the virus – and Sacha wasn’t convinced combining them would work any better. Sacha has worked for years to develop leronlimab, which is designed to block HIV from entering immune cells through a surface protein called CCR5. His longtime OHSU colleague and coauthor Nancy Haigwood, PhD, thought combining existing therapies with leronlimab might be effective.

The study that published today shows she was correct.

Haigwood, a former professor and ONPRC director, is a virologist and immunologist who has specialised in HIV antibody research for decades. “We were astounded and overjoyed, actually,” Haigwood said. “It’s a remarkable result.”

Antiretroviral therapy has already been approved in people, whereas broadly neutralising antibodies and leronlimab are both being tested separately in clinical trials. This new discovery of a one-time, three-part regimen to clear the virus in newborn babies would first need to be tested in clinical trials in people – most likely in newly exposed adults initially – before it would be widely available to constrain an HIV epidemic that continues to kill 600 000 people worldwide each year.

Researchers say they are optimistic, given the anatomical similarity between nonhuman primates and people.

“There was no reason to think this would completely clear the virus,” Sacha said. “It’s one of those things where you test it and, holy cow, it works and you’ve discovered something new.”

Exactly how this approach worked remains unclear, but Sacha and Haigwood said it appears that the combination of therapies is far more potent and effective than each therapy alone. The key appears to be leronlimab’s ability to block HIV from entering immune cells through the surface protein CCR5.

“For reasons we don’t understand, HIV really wants to use CCR5 receptors to infect cells,” Sacha said. “By blocking access, it’s like you’ve kept fuel away from the fire.”

Haigwood uses a slightly different analogy:

  • Turning off the faucet: Antiretroviral therapy doesn’t eliminate HIV altogether, but it minimises its ability to replicate.
  • Mopping up: Neutralising antibodies effectively corral HIV so there is less virus circulating in the body’s blood supply.
  • Sealing off: Leronlimab blocks what’s left of the virus from infecting immune cells – the equivalent of sealing off the room with a water-tight valve.

Haigwood believes the combination appears to be especially potent early in the infection.

“There’s a lot more going on during the first week of infection than we previously thought,” she said. “From this experiment, it looks like there’s a dynamic interaction between the virus and antibodies that takes place as the virus begins to spread.”

Researchers are eager to see whether the combined regimen can be effective beyond 72 hours of the initial infection.

“We only tested out to three days,” Sacha said. “Could it work a week after infection? Two weeks? How far can you go after infection, and still purge the virus?”

By Erik Robinson

Source: Oregon Health & Science University

Categories : Paediatrics Respiratory DiseasesTags :

New Clues Raise Hopes for Better Treatment of RSV in Babies

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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.”

Source: University College London

Categories : PaediatricsTags :

Postnatal Collapse is Rare but Can Have Deleterious Consequences

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Photo by Duda Oliveira

Sudden unexpected postnatal collapse during the first week of life is rare but can have deleterious consequences. A new study from Karolinska Institutet shows that the condition is more common than previously estimated and highlights measures that may reduce the risk.

Sudden unexpected postnatal collapse (SUPC) occurs when an apparently healthy newborn suddenly stops breathing and collapses during the first week of life. In a new study, published in the journal Acta Paediatrica, researchers investigated how common the condition is and when it occurs. 

The researchers analysed approximately 483 000 births at seven maternity units in Stockholm between 2002 and 2022 and identified 149 cases of SUPC. This corresponds to 31 cases per 100 000 live births. 

“It is important to remember that this is a very rare condition. According to our findings, it affects around 30 infants each year in Sweden, and two to four of these cases lead to death. Most cases occur during the infant’s first day of life,” says the study’s senior author, Eric Herlenius, paediatrician at Karolinska University Hospital and Professor of Paediatrics at the Department of Women’s and Children’s Health, Karolinska Institutet. 

The study found that 81 per cent of collapses occurred during the first 24 hours after birth, with half taking place within four hours of delivery. Seven per cent of affected infants died and 26 per cent sustained permanent neurological injuries. Two-thirds of the cases occurred while the infant was sharing a bed with a parent.

“Skin-to-skin contact is important for newborn infants, but parents need to ensure that the baby’s airways are always clear and visible. Adults should not fall asleep while holding their baby skin to skin, and infants should not sleep in the same bed as their parents during the first three months of life,” says Eric Herlenius

The researchers point out that SUPC still lacks a specific diagnostic code, making the condition difficult to monitor. According to the researchers, this may have contributed to an underestimation of its true incidence. 

Reviewed medical records

To identify cases, the researchers reviewed electronic medical records of infants born after at least 35 weeks of pregnancy. The records were searched for symptoms suggestive of collapse, such as episodes of apnoea, bluish skin discolouration, or sudden loss of muscle tone. Each suspected case was then assessed according to internationally established criteria for SUPC.

Since 2011, the researchers have also collected urine samples from affected infants and compared them with samples from healthy infants of the same age. They found higher levels of a prostaglandin E2 metabolite in infants who experienced SUPC during the first days of life, the same period during which most collapses occurred

“We believe that clearer guidelines for safe skin-to-skin care and safe sleep environments are needed and could help reduce the number of cases further,” says Eric Herlenius. 

At the same time, the researchers aim to improve understanding of the biological mechanisms underlying the condition, including the elevated levels of prostaglandin E2 metabolite observed in some affected infants. By studying the relationship between these levels and the brainstem’s control of breathing, the researchers hope to gain a better understanding of why some newborns develop SUPC and, in some cases, sudden unexpected death. 

Source: Karolinska Institutet

Categories : PaediatricsTags :

Study Finds No Link Between Newborn Upper Lip Frenulum and Breastfeeding Difficulties

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A joint study by the University of Oulu and Oulu University Hospital in Finland suggests that a newborn’s upper lip frenulum is unlikely to be a major cause of breastfeeding difficulties.

The study, published in JAMA Network Open, followed 264 mother–infant pairs at Oulu University Hospital between 2023 and 2024. Researchers assessed the anatomy and mobility of the upper lip frenulum in healthy, full-term infants and compared the findings with mothers’ reported breastfeeding experiences.

Overall, 86% of mothers reported experiencing breastfeeding difficulties during the first days of breastfeeding. However, based on data collected in the six-month follow-up questionnaire, the researchers found no association between the anatomical characteristics of the upper lip frenulum and breastfeeding problems. The thickness of the frenulum, its attachment site, or other structural features did not increase the risk of breastfeeding difficulties.

Instead, previous breastfeeding experience appeared to be beneficial for breastfeeding. Breastfeeding problems were reported less frequently among mothers with experience of breastfeeding previous children.

According to the researchers, an upper lip frenulum that interferes with breastfeeding is a rare finding. Nevertheless, the number of lip-tie release procedures has increased in several countries in recent years, despite limited evidence supporting their benefits.

“Breastfeeding difficulties in newborns should always be assessed comprehensively,” said paediatrician and neonatologist Outi Aikio. “Based on our findings, we found no evidence to support upper lip frenulum surgery in healthy, full-term infants. Instead, I would emphasise the importance of high-quality breastfeeding support, particularly in the early weeks after birth, when breastfeeding challenges are common.”

Source: University of Oulo

Research article: Niemelä L, Lohi V, Aitamurto S, Lehtinen A, Aikio O. Upper Lip Frenulum Findings and Breastfeeding Problems in Healthy Newborns. JAMA Netw Open. 2026;9(5):e2613308.

Categories : Infection Control Neurology PaediatricsTags :

New Treatment Aims to Prevent Meningitis Without Antibiotics

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Meningitis is rare in newborns but often life-threatening and can cause serious and lasting damage, including developmental problems. Now, researchers from ETH Zurich and the University of Basel have developed an approach that seeks to prevent transmission to newborns. The research is published in Nature Communications.

Although meningitis is thankfully rare in newborns as a whole, it is more common in premature babies, affecting one in every 500 such infants in industrialised economies and likely more in developing countries. One of the leading pathogens responsible for these meningitis cases is the K1 form of the E. coli bacterium. In the adult intestine: in one in three healthy adults, E. coli K1 is part of the intestinal flora. As a silent cohabitant, the bacterium causes no problems in this environment. It is kept in check by other bacteria and a functioning immune system.

However, if the pathogen is carried by an expectant mother, it can be transmitted to the child during birth and enter its intestine. In premature babies whose immune systems are still weak, the pathogen can enter the bloodstream and migrate to the brain, where it causes severe inflammation.

First weaken the pathogen, then fight it

Researchers led by Emma Slack, Professor of Mucosal Immunology at ETH Zurich, and Médéric Diard, Professor of Infection Biology at the Biozentrum of the University of Basel, want to stop transmission from happening in the first place. Their idea is to eliminate the pathogen in pregnant women who carry it in their intestine – but that’s easier said than done.

A year ago, the two researchers from Zurich and Basel had already jointly developed a concept for eradicating other pathogens living in the intestine (as ETH News reported). Back then, they used a combination therapy with two components: an oral vaccination that weakens the pathogenic bacterium, followed by a dose of harmless microbes that compete with the weakened pathogen for food, starve it out, and ultimately supersede it. In experiments on mice, the researchers demonstrated that this approach can eliminate certain salmonellas and E. coli strains in the intestine.  

So tough that three components are needed

However, the K1 form of E. coli is a formidable opponent: unlike other E. coli bacteria, it is protected by a slippery outer layer. This prevents the antibodies generated by the oral vaccination from attacking the bacterium.

The team of researchers led by Slack and Diard therefore extended its previous two-pronged approach with a third component known as bacteriophages (or simply phages). These are viruses that specifically infect and kill bacteria.

However, the bacteria can make changes to themselves in order to evade the danger posed by these viruses. The phages attack the bacteria by docking to the protective layer, and the bacteria seek to prevent this by undergoing a sort of rapid evolution in which this layer is disposed of. Rapid in this case means that, since the bacteria are so numerous and multiply so quickly, they need fewer than 24 hours to adapt. 

“This is essentially a resistance mechanism that the bacteria deploy against the phages,” says Slack. “We use this mechanism to our advantage: the antibodies formed by the oral vaccination are effective against K1 bacteria that no longer have their protective coating.”

Most young animals protected

The project involved searching for effective strains of phages. Scientists generally find phages in places that are home to lots of bacteria: nutrient-rich bodies of water, the intestinal flora or, very often, waste water and waste water treatment plants. When it comes to the phages used in this study, the researchers from the Biozentrum in Basel found what they were looking for in waste water samples from the treatment plant of the Lucerne conurbation. From such a sample, their lab work successfully isolated several phages that are particularly effective at attacking the bacterium E. coli K1.

In experiments with pregnant mice, which the researchers had previously infected with pathogenic E. coli K1, they were able to demonstrate the effectiveness of their triple-pronged treatment. The researchers first gave the mice phages that forced the bacteria to cast off their protective shell. Second, they administered an oral vaccination that produced antibodies in the intestine in order to weaken the bacteria. Third, they gave them a harmless probiotic bacterium that could compete against the weakened bacteria and occupy their ecological niche in the intestine.

In a control experiment in which the researchers did not treat the mothers, E. coli K1 was transmitted to 83% of young animals at birth. By contrast, the triple-pronged treatment significantly reduced the level of E. coli K1 in the mothers’ intestines, such that the pathogen was only transmitted to 23% of the young animals. The remaining offspring were protected.

Works even when antibiotics fail

The researchers are now keen to continue with their approach in order to develop a treatment for humans. In a world in which effective antibiotics are becoming increasingly scarce, we need new therapeutic approaches, says Slack. “Bacteria such as E. coli K1 are difficult to tackle. Our approach is potentially the only one that can be used to fight this pathogen and others without antibiotics.”

Not only can E. coli K1 cause cases of meningitis in newborns, which today must be treated with antibiotics in a race against time. It is also one of the most frequent causes of cystitis and pyelitis – infections that can also lead to serious cases of sepsis. 

The ETH professor doesn’t perceive any major obstacles to developing an effective treatment for humans: “Oral vaccinations, probiotics and even phages are all already used in medicine,” she says. It will also be possible, she adds, to pack all three components into a single capsule that people can simply swallow.

Moreover, the scientists are planning projects in which they want to use the same approach to tackle bacteria other than E. coli K1, including multi-resistant pathogens, against which many antibiotics are no longer effective.

Source: ETH Zurich

Categories : PaediatricsTags :

WHO Prequalifies First-ever Malaria Treatment for Infants

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Ahead of World Malaria Day on 25 April, the World Health Organization (WHO) has announced a significant step forward in the fight against malaria with the prequalification of the first treatment developed specifically for newborns and young infants weighing between two and five kilograms. The prequalification designation indicates that the medicine meets international standards of quality, safety and efficacy, and will help to expand access to quality-assured treatment for one of the most underserved patient groups.

The newly prequalified treatment, artemether-lumefantrine, is the first antimalarial formulation designed specifically for the youngest malaria patients. Until now, infants with malaria have been treated with formulations intended for older children, which increase the risk of dosing errors, side effects and toxicity. WHO prequalification will enable public sector procurement, contributing to closing a long-standing treatment gap for some 30 million babies born each year in malaria-endemic areas of Africa.

“For centuries, malaria has stolen children from their parents, and health, wealth and hope from communities,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “But today, the story is changing. New vaccines, diagnostic tests, next-generation mosquito nets and effective medicines, including those adapted for the youngest, are helping to turn the tide. Ending malaria in our lifetime is no longer a dream – it is a real possibility, but only with sustained political and financial commitment. Now we can. Now we must.”

New prequalified tests

On 14 April 2026, WHO also prequalified three new rapid diagnostic tests (RDTs) designed to address emerging diagnostic challenges for malaria. The most common malaria RDTs for P. falciparum parasite work by detecting the protein, known as HRP2. But based on reported studies and surveys in 46 countries, some strains of the malaria parasite have lost the gene that makes this protein – so they become “invisible” to HRP2-based RDTs, leading to false-negative results. In countries in the Horn of Africa, up to 80% of cases were missed, leading to delayed treatment, severe illness, and even death.

The new tests address this issue by targeting a different parasite protein (pf-LDH) that the malaria parasite cannot easily shed. They provide a reliable, quality-assured alternative where HRP2-based tests are failing. WHO now recommends that countries switch to these alternative RDTs when more than 5% of cases are missed due to pf-hrp2 deletions. This ensures accurate diagnosis, appropriate treatment, and protects hard-won malaria control gains – especially for the most vulnerable communities.

Source: World Health Organization

Categories : Paediatrics Pain ManagementTags :

Sugar Comforts Newborn Babies During Painful Procedures

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Researchers have found that sucrose can relieve newborn babies’ pain during common hospital procedures

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A new Cochrane review has found that sucrose can help with pain relief in newborn babies during common hospital procedures, such as venepuncture. This involves drawing blood with a needle, typically for testing. 

Newborns, especially preterm infants in neonatal intensive care units (NICUs), undergo numerous painful procedures. Because of their immature pain regulation, they can experience these procedures intensely. Preventing and treating procedural pain in hospitalized newborns is important, as repeated untreated pain has been associated with poorer physical growth and potential effects on brain development.

Accessible, low-cost solutions such as sucrose – a sweet sugar solution placed in a baby’s mouth shortly before needle procedures – have been used for decades. However, evidence specific to some procedures, such as venepuncture, has been limited.

Despite sucrose being recommended in multiple guidelines for procedural pain relief in infants, its use in clinical settings remains inconsistent.

Low-cost, safe intervention

The new review examined 29 clinical trials involving more than 2700 preterm and full-term babies undergoing venepuncture in hospital. It found that sucrose probably reduces pain during and immediately after the needle procedure when compared to no treatment, water or standard care. The findings also suggest that sucrose works especially well when combined with non-nutritive sucking, such as a pacifier or dummy. 
 

“Newborn babies undergo frequent needle procedures in hospital without any pain relief or comforting measures, even though older children and adults rarely have these procedures done without pain care.

The evidence shows that a small amount of sucrose given just before the procedure is a simple, fast and effective way to reduce that pain. Our review helps clinicians use this evidence more confidently and consistently in practice.”

— Mariana Bueno, University of Toronto


None of the studies included in the review reported immediate side effects from sucrose when used in the small amounts required for pain relief. However, the studies focused on short-term effects, and more research is needed to understand any potential long-term effects of repeated use in babies who spend extended time in neonatal care.
 

“Parents may be surprised to learn that something as simple as a few drops of sugar solution can make a real difference to their baby’s comfort during blood tests. 

This is a low-cost, safe intervention that works within minutes, and it can be especially helpful when other comforting methods like skin-to-skin contact or breastfeeding aren’t possible.”

— Ligyana Candido, University of Ottawa

Treated like other medications

Although sucrose is already widely used in neonatal units, the researchers found considerable variation in how it is given, including differences in dose and timing. 

Bueno added:
 

“What stood out to me when doing this review was the wide variation in how sucrose was given to newborns.”


The authors suggest the findings can help inform clearer clinical protocols and more consistent practice.

They also highlight that sucrose should be used purposefully for painful procedures and documented appropriately, rather than being given routinely to settle a crying baby. 


“To ensure safety and clinical consistency, sucrose must be administered under formal medication protocols that define specific timing and dosage for painful procedures.”

— Jiale Hu, Virginia Commonwealth University


The review authors say future research should focus on comparing effective comfort measures such as skin-to-skin contact, breastfeeding and sucrose with each other, rather than continuing to compare them to no treatment, and on understanding any potential long-term effects of repeated use in babies who spend extended time in neonatal care. 

By Mia Parkinson

Read the review

Source: Cochrane